Progress

Review

Groups

Pancreatic Cancer: 

An Agenda for Action 

Report of the Pancreatic Cancer 

Progress Review Group 

February 2001
Pancreatic Cancer: An Agenda for Action

Report of the Pancreatic Cancer Progress Review Group 

February 2001 
From the Leadership 

It is a great pleasure to submit this Report of the Pancreatic Cancer Progress Review Group 

(PRG) to the Director and Advisory Committee to the Director of the National Cancer Institute 

(NCI). To accelerate progress against pancreatic cancer, the Director, NCI, requested the PRG to 

identify scientific priorities and needs so that the Institute can forge a national agenda for 

research on this disease. This report is the outcome of the PRG’s 10-month effort to carry out this 

charge. 

Although pancreatic cancer is less common than some other cancers, it is nearly always fatal, so 

we appreciate the NCI’s decision to institute a PRG to address it. The PRG’s report demonstrates 

a need to expand pancreatic cancer research aggressively in almost all areas: biology, etiology, 

prevention, diagnosis, treatment, control, and perhaps most importantly, training and 

infrastructure. However, rather than propose a long list of recommendations, the PRG proposes a 

limited set of them that truly represent the highest priorities in the field. The PRG was able to 

accomplish this goal by using a structured, formal process at its Roundtable Meeting in which 

participants integrated the findings from specific breakout groups into the deliberations of more 

broad ones. The result of this approach, we believe, is a report that is clear and concise in its 

recommendations. 

We believe that the hard work of this PRG has resulted in recommendations that, if pursued, will 

do much to eradicate morbidity and mortality due to pancreatic cancer. We look forward to 

assisting the NCI in implementing these recommendations and to following their progress. 

Respectfully, 

Scott Kern, M.D. Margaret Tempero, M.D. 

Co-Chair, PRG Co-Chair, PRG 

National Cancer Institute 

Barbara Conley, M.D. 

Executive Director, PRG 
We the undersigned members of the Pancreatic Cancer Progress Review Group concur 

with the enclosed report. 

Scott Kern, M.D. Margaret Tempero, M.D. 

Co-Chair Co-Chair 

Barbara Conley, M.D. 

Executive Director, PRG 

James Abbruzzese, M.D. N. Volkan Adsay, M.D. 

Teri Brentnall, M.D. Arthur Charnsangavej, M.D. 

Paul J. Chiao, Ph.D. Douglas B. Evans, M.D. 

Jorge Gomez, M.D., Ph.D. Louise Grochow, M.D. 

Ernie Hawk, M.D., M.P.H. Michael Anthony Hollingsworth, Ph.D. 

Elizabeth A. Holly, Ph.D., M.P.H. Ralph H. Hruban, M.D. 
We the undersigned members of the Pancreatic Cancer Progress Review Group concur 

with the enclosed report. 

Elizabeth M. Jaffee, M.D. 

Charles Lightdale, M.D. 

Martin McMahon, Ph.D. 

Cherie Nichols, M.B.A. 

Gloria Petersen, Ph.D. 

Selwyn Maurice Vickers, M.D. 

David Whitcomb, M.D., Ph.D. 

Murray Korc, M.D. 

Albert B. Lowenfels, M.D. 

Michael L. Meyers, M.D., Ph.D. 

Dan O’Hair, Ph.D. 

Paula Simper 

Robert Vizza, Ph.D. 
Acknowledgments 

This report is the result of 10 months of intense work, drawing upon the combined skills and 

efforts of many people. The PRG would like to extend special thanks to the following: 

• The researchers, clinicians, and members of the advocacy community who participated in the 

Pancreatic Cancer Roundtable Meeting. The recommendations of the PRG are the result of 

their expertise, insight, and effort. 

C Lisa Begg, Randall Brand, William Brugge, Carolyn Compton, Ron Depinho, William Lee, 

Robert Radinsky, Mace Rothenberg, Vito Quarranta, Debra Silverman, Joel Tepper, and 

Charles Ulrich, who served with us as speakers and co-chairs for breakout sessions at the 

Roundtable Meeting. We are indebted to them for serving in this capacity so well. 

C Kevin Callahan, Annabelle Uy, Kate Nagy, and Terri Hallquist, who, as staff of the NCI’s 

Office of Science Planning and Assessment, provided strong guidance and technical support 

throughout the life of the PRG. 

C Suzanne Reuben, who, as lead science writer, provided expert advice and knowledge while 

working steadfastly with us for months to draft this report. 

C Randi Henderson, Alice Lium, Cheryl Pellerin, Paul Phelps, Barbara Shapiro, and Nancy 

Volkers, who, as science writers, provided exceptional writing support at the Roundtable 

Meeting. 

C Josette Johnson, Audrey Thomas, Robert Wald, and their colleagues at Palladian Partners, 

who provided logistical support to the PRG from its first meeting to its last, and provided 

expertise for the design, formatting, and printing of this report. 
Table of Contents

Executive Summary ............................................................1

Section I: Health of the Field and Overarching Issues ..................................7

Section II: Research Priorities

Tumor Biology ............................................................11

Risk, Prevention, Screening, and Diagnosis .....................................18

Therapy .................................................................23

Health Services Research ....................................................27

Section III: Scientific Toolkit ....................................................31

Appendices

Pancreatic Cancer Progress Review Group

Member Roster ......................................................35

Roundtable Participant Roster ..........................................37

NCI-Supported Pancreatic Cancer Research .....................................41

About the National Cancer Institute’s Progress Review Groups ......................43
Executive Summary
Executive Summary

Pancreatic cancer is a devastating disease 

that swiftly robs patients of both quality and 

quantity of life. It is the fifth leading cause 

of cancer death in the United States. In 2001, 

an estimated 29,200 new cases will be 

diagnosed, and 28,900 people will die from 

the disease. Most of these tumors will be 

ductal adenocarcinomas, from which there 

currently is little chance of long-term 

survival—median survival is six months or 

less, and only four percent of patients are 

alive five years after diagnosis. Given its 

incidence and almost universal fatality, 

substantially increased research efforts are 

clearly warranted to understand, prevent, and 

control this disease. 

Pancreatic cancer has been understudied in 

both basic research laboratories and the 

clinic. In terms of total research dollars, total 

numbers of researchers, and numbers of 

researchers who are highly focused on this 

disease, pancreatic cancer lags significantly 

behind all of the most common tumors, 

despite their far more favorable survival 

rates. For example, in 1999, pancreatic 

cancer research received only $17.3 million 

in National Cancer Institute (NCI) funding. 

Severely limited funding for pancreatic 

cancer research has likewise limited the size 

of the research community pursuing progress 

against any aspect of the disease, and the 

number of researchers who are able to make 

pancreatic cancer their principal research 

focus. In 1999, of the 270 grants recorded by 

the NCI as relevant to pancreatic cancer, less 

than three dozen were at least 50 percent 

relevant to research on the disease. 

Available data suggest that fewer than ten 

principal investigators have multiple grants 

or a primary career focus on pancreatic 

cancer. 

Research over the past decade indicates that 

pancreatic cancer is sufficiently distinctive 

in its etiology, pathogenesis, and clinical 

behavior to justify a major expansion of 

investigations focused primarily on this 

disease, and that such research can be 

accomplished with reasonable efficiency. 

Greater commitment of resources and 

scientific expertise are needed to achieve 

significant improvements in pancreatic 

cancer diagnosis and management. 

To help develop a national agenda for 

pancreatic cancer research, the Director, 

NCI, requested that a multidisciplinary 

Progress Review Group (PRG) on pancreatic 

cancer analyze the NCI’s current research 

portfolio on the disease and develop and 

prioritize recommendations for achieving 

progress. This report details the outcome of 

that effort. 

THE PRG PROCESS AND 

DEVELOPMENT OF THE PRG 

REPORT 

PRG members included prominent members 

of the scientific, medical, industry, and 

advocacy communities, representing the full 

spectrum of expertise required to make 

comprehensive recommendations for NCI’s 

pancreatic cancer research agenda. At a 

Planning Meeting held in May 2000, the 

Pancreatic Cancer PRG organized a 

Roundtable to consider progress and identify 

issues, barriers, and needs across the 

continuum of pancreatic cancer research. 

The group was instructed to prioritize 

suggestions for new research efforts over the 

next five to ten years. Roundtable 

participants were identified and topics were 

selected for breakout sessions, to which the 

Roundtable participants were assigned. PRG 

Executive Summary 1 
members served as co-chairs for the 

breakout sessions. 

The Pancreatic Cancer PRG Roundtable of 

approximately 120 participants met on 

September 15–17, 2000 in Chantilly, 

Virginia. Following initial plenary 

presentations on the state of the art in 

pancreatic cancer tumor biology, 

risk/prevention/detection, and therapy, 

Roundtable participants broke into initial 

discussion sections addressing Pathology 

and Tissue Characterization, Signaling, 

Stromal Interactions, Risk, Diagnostic 

Technologies, and Host/Tumor Interactions. 

Overarching resource needs were discussed 

subsequently in sessions covering the 

Scientific Toolkit and Clinical Trials 

Networks. Scientific priorities, related 

recommendations, and specific resource 

needs were then established and prioritized 

in sessions on Tumor Biology, 

Risk/Prevention/Screening/Diagnosis, 

Therapy, and Health Services Research. A 

panel discussion on Career Development 

and Funding also was held. 

The PRG used input from the Roundtable to 

delineate and prioritize recommendations for 

research directions, related scientific 

questions, and resource and infrastructure 

needs. There was a high degree of agreement 

on many of the crucial needs of the field. In 

support of the process, NCI also provided 

the PRG with an analysis of its current 

pancreatic cancer research portfolio that 

assisted the PRG in developing its 

recommendations. 

ORGANIZATION OF THE REPORT 

The full report of the Pancreatic Cancer 

PRG is presented in three sections. Section I, 

Health of the Field and Overarching Issues, 

addresses current research and funding 

levels for pancreatic cancer and critical 

issues such as manpower development and 

training needs, and resource deployment and 

organization. 

Section II details Research Priorities in four 

principal scientific areas of pancreatic 

cancer research: 

• Tumor Biology 

• Risk/Prevention/Screening/Diagnosis 

• Therapy 

• Health Services Research 

Section III enumerates key resources, or a 

Scientific Toolkit, that the PRG believes are 

urgently needed to accelerate achievement of 

the research priorities. Requests for 

components of the Toolkit were often 

echoed among the recommendations related 

to the research priorities described in 

Section II. 

A rationale is provided for each priority and 

resource identified in these sections. Three 

appendices also are included. Appendix A is 

a roster of the Pancreatic Cancer PRG 

members and Roundtable participants. 

Appendix B describes NCI-supported 

pancreatic cancer research. A detailed 

description of the purpose and process of 

NCI’s Progress Review Groups is included 

as Appendix C. 

Sections I, II, and III of the full PRG report 

are summarized below. 

I. Health of the Field and Overarching 

Issues 

Pancreatic cancer research currently suffers 

from a variety of unmet training, career 

development, and organizational needs. 

Very few researchers are dedicated to 

pancreatic cancer research at any level. In 

addition to these serious limitations, the 

pancreatic cancer research field suffers from 

several challenges, such as low levels of 

NCI funding, that historically have resulted 

2 Pancreatic Cancer: An Agenda for Action 
in low levels of enthusiasm for pancreatic 

cancer research among physician-scientists. 

Action is needed to significantly augment 

pancreatic cancer research overall by: 

• Developing sustained, expanded training 

and career development efforts in 

pancreatic cancer research and care. 

• Creating an interdisciplinary 

coordinating mechanism to monitor 

funding patterns and identify funding 

deficits and opportunities in pancreatic 

cancer research. 

• Establishing centers of excellence for 

pancreatic cancer research and care. 

II. Research Priorities 

Tumor Biology 

Pancreatic cancer is a unique and 

heterogeneous disease that is difficult to 

study. Molecular aspects of normal cell 

differentiation and development of the 

pancreas are poorly understood. Molecular 

processes involved in the development of 

benign and malignant pancreatic diseases are 

known in part, although the nature and 

origin of the precursor cells for pancreatic 

cancer have not been delineated. The 

relationships between differing clinical 

presentations of pancreatic cancer, 

prognosis, and the mechanisms of drug 

resistance are undefined. The contribution of 

the tumor’s supportive tissue matrix 

(stroma) and other host factors to patient 

prognosis has not been studied. Wellcharacterized tissue of sufficient quality for 

molecular analysis, particularly for early 

lesions, is scarce. The PRG identified four 

research priorities: 

• Achieve a more complete understanding 

of the normal biology of the pancreas. 

• Elucidate the development of pancreatic 

adenocarcinoma. 

• Study the natural history of the 

pancreatic cancer stroma and the 

formation of reactive tissue in the stroma 

in response to the presence of a tumor 

(desmoplasia). 

• Investigate clinically important hosttumor interactions and develop new 

therapeutic strategies to address them. 

Two resources critical to this research are: 

• Specimen banks of normal, proliferative, 

precancerous, and cancerous human 

pancreatic tissue. 

• Experimental model systems. 

Risk/Prevention/Screening/Diagnosis 

Pancreatic cancer patients seldom exhibit 

disease-specific symptoms until the cancer is 

at advanced stages, and tumors 1–2 cm in 

size often have already spread beyond the 

local area of the primary tumor. For these 

reasons, determining risk factors (genetic, 

environmental and gene-environment 

interactions), and developing preventive 

strategies and improved detection 

technologies are critically important. The 

three most important research priorities are 

to: 

• Identify genetic factors, environmental 

factors, and gene-environment 

interactions that contribute to pancreatic 

cancer development. 

• Develop, implement, and evaluate 

approaches to prevent pancreatic cancer 

in high-risk cohorts (e.g., familial 

pancreatic cancer, hereditary 

pancreatitis). Studies should be 

performed in humans and in animal 

Executive Summary 3 
models of early neoplasia (e.g., PanIN3). 

• Identify and develop surveillance and 

diagnosis methods for the early detection 

of pancreatic cancer and its precursors. 

Seven critical resources include: 

1. New and expanded registries for: 

— Identification of high-risk patients 

and kindreds. 

— Linkage analysis. 

— Tissue and specimen resources. 

— Identification of screening and 

surveillance cohorts. 

— Epidemiologic assessment of geneenvironment interactions. 

2. Specimen banks for all types of 

biomaterials (e.g., blood, serum, 

pancreatic juice, stool, tumors, other 

body fluids). 

3. Consortia of large, aging cohorts for 

pooled analyses to elucidate causal 

factors. 

4. Education for providers and 

investigators about pancreatic cancer risk 

assessment, evaluation protocols, and 

sample collection. 

5. A Web-based imaging library to serve as 

an educational tool, research tool, 

reference standard for imaging studies, 

and source of images for the application 

of new technologies such as artificial 

intelligence and other post-imaging 

processing. 

6. Technology centers for comprehensively 

assessing gene and protein expression 

for use in identifying biologic indicators 

of the presence and behavior of 

pancreatic cancer and its precursors. 

7. Animal models for the study of 

environmental factors, gene-environment 

interactions, chemoprevention, 

chemotherapy, radiation therapy, 

vaccines, and imaging. 

Therapy 

A number of inherited and acquired tumorassociated gene alterations present in 

pancreatic cancer have been identified, but 

significant gaps exist in our understanding 

of how these alterations occur in pancreatic 

cancer development, affect the interaction of 

signaling proteins in the course of the 

cancer, and influence molecular interactions 

between tumor and host. It remains a 

challenge to better understand and determine 

how the molecular biology of pancreatic 

cancer can be harnessed for therapeutic gain. 

Three research priorities are to: 

• Facilitate the discovery and development 

of targeted therapeutics. 

• Facilitate development of preclinical and 

minimally invasive clinical techniques to 

assess targeted therapeutics. 

• Accelerate research into the supportive 

care of patients with pancreatic cancer. 

Three critical resources are needed for this 

research: 

1. Mechanisms to facilitate investigator 

access to targeted therapeutic agents for 

preclinical studies and clinical trials. 

2. Infrastructure for molecular target 

assessment. 

3. Infrastructure for multidisciplinary 

clinical trials and promoting patient 

participation. 

4 Pancreatic Cancer: An Agenda for Action 
Health Services Research 

Health services research (HSR) is crucial in 

pancreatic cancer to help ensure that 

patients, families, and health care providers 

are well informed about all aspects of the 

disease. NCI’s recent enhanced commitment 

to cancer communications initiatives 

provides new opportunities for HSR relative 

to pancreatic cancer. Advances in tumor 

biology, diagnosis, and treatment can be 

expected to promote more hopeful and 

positive attitudes toward pancreatic cancer 

and assist in fulfilling HSR research 

priorities. Four key priorities are to: 

• Identify effective forms of health care 

provider communication with pancreatic 

cancer patients. 

• Identify determinants of message 

effectiveness in aiding decision making 

by patients. 

• Identify manpower requirements and 

costs of multidisciplinary clinical trials 

in pancreatic cancer. 

• Determine the efficacy of current 

practices in pancreatic cancer diagnosis 

and care and evaluate the impact of 

improvements in the management of 

difficult treatment and end of life issues. 

The PRG identified four categories of 

critical resources: 

1. A survivorship registry to enable the 

study of relationships among survival, 

biological (e.g., genes, markers), and 

self-report data, beginning at diagnosis 

and continuing though follow-up care. 

2. A Web-based repository to track, update, 

and categorize information on the costs 

of clinical trial research focusing on 

pancreatic cancer. 

3. New models that can be applied and 

validated in community and academic 

research settings, including those for: 

— Analyzing cost and level of effort 

required to conduct clinical research 

in pancreatic cancer. 

— Assessing communication 

effectiveness. 

— Improving patient decision making. 

— Describing and summarizing 

consistent patterns of variables 

indicative of longer term survival of 

pancreatic cancer. 

— Characterizing quality of life and end 

of life parameters for pancreatic 

cancer patients. 

4. Education, training, and communication 

tools: 

— Communication toolkits for health 

care providers with education 

components and collateral materials, 

particularly to assist/support patient 

decision making. 

— Patient decision making toolkits for 

various patient populations. 

— Mechanisms to facilitate increased 

interaction among health care 

providers, advocates, and 

professional and funding 

organizations. 

III. Scientific Toolkit 

The lack of six key resources and tools poses 

a major impediment to progress in 

pancreatic cancer research: 

1. A specimen resource to provide access 

to a range of normal and neoplastic 

human pancreas samples. 

2. A relational database containing 

information on the biological profiles of 

normal and neoplastic pancreas cells. 

Executive Summary 5 
3. New biological sampling techniques that 

permit analysis of minute quantities of 

biological samples. 

4. Organization of growing knowledge 

about signaling pathways into 

interrelated networks and systems to 

assess the ultimate outcome of 

alterations in pathways important in 

pancreatic cancer. 

5. In vivo and ex vivo gene-based model 

systems that faithfully parallel the 

complex biology of human pancreatic 

adenocarcinoma. 

6. Imaging systems for elucidating the 

biology of pancreatic cancer, detecting 

disease, and monitoring patients after 

therapeutic intervention. 

CONCLUSION 

The Pancreatic Cancer PRG believes that 

urgently needed progress against pancreatic 

cancer must be achieved through a concerted 

and significant effort to build a 

comprehensive research community focused 

on this disease. To be effective, this 

community must have stable support and the 

scientific depth and diversity to challenge 

the disease comprehensively, including, but 

not limited to: the nature of normal pancreas 

biology, individual risk assessment, 

surveillance for early disease, diagnosis, 

prognosis assessment, effective therapy, and 

beneficial health service design and delivery, 

including communication mechanisms. The 

PRG has identified critical opportunities. A 

greater research emphasis on this cancer, 

incorporating the suggestions contained in 

the full report of the Pancreatic Cancer PRG, 

is essential to take full advantage of these 

opportunities. 

6 Pancreatic Cancer: An Agenda for Action 
I. Health of the Field

and 

Overarching Issues 
Health of the Field and Overarching Issues

Pancreatic cancer is disproportionately 

underrepresented in both clinical and basic 

research compared with other cancer sites. 

Several factors may be contributing to this 

marginal research base in pancreatic cancer. 

Scientific investigators with interest and 

expertise in this area comprise a very small 

cadre. Pancreatic cancer care is complicated, 

requiring a multidisciplinary approach, and 

despite our best efforts, outcomes are nearly 

always disappointing. To build a robust 

laboratory, clinical, and population science 

research program for this disease demands 

unusual effort that currently is made more 

difficult by a lack of key resources, such as 

appropriate preservation of pancreatic tissue 

and key reagents for translational studies. 

No specialized scientific infrastructure exists 

to support training or funding for pancreatic 

cancer research. Yet novel approaches and 

unique commitments will be necessary to 

make progress against pancreatic cancer. 

Advances in other diseases suggest that 

increased investment in pancreatic cancer 

research can be expected to yield dramatic 

progress. 

Steady increases in the National Institutes of 

Health (NIH) and National Cancer Institute 

(NCI) budgets have translated into 

significantly greater funding for research on 

diseases such as breast, colorectal, and 

prostate cancer. Pancreatic cancer research 

funding, however, has not experienced 

similar growth. In 1999, pancreatic cancer 

research received only $17.3 million in NCI 

funding. 

Available data do not lend themselves to a 

precise assessment of the funding deficit in 

pancreatic cancer research, but figures 

derived by the PRG from these data outline 

basic trends. For example, very few 

investigators focus exclusively on pancreatic 

cancer. Of slightly more than a dozen 

principal investigators currently holding 

multiple grants related to pancreatic cancer, 

fewer than six have a clear focus on 

pancreatic adenocarcinoma. Of the nearly 

two dozen grants with major relevance to 

pancreatic adenocarcinoma in 1995, just 

under a dozen of these same investigators 

still held these grants in 1999. These figures 

suggest either a striking lack of career 

commitment to pancreatic cancer research, 

or other serious barriers such as a lack of 

funding and/or other resources that makes 

such commitment difficult. 

In 1999, of the 270 funded grants recorded 

as relevant to pancreatic cancer, fewer than 

three dozen were at least 50 percent relevant 

to research on pancreatic adenocarcinoma. 

Though discouraging, this reflects an 

improvement over previous years (1990 and 

1995). Most grants recorded as relevant to 

pancreatic cancer had only minor fractions 

of effort devoted to the disease, with the 

majority of effort devoted to research on 

other cancers. Moreover, many of the grants 

for research on pancreatic adenocarcinoma 

are relatively small in size and exploratory. 

These data illustrate the serious 

underfunding of pancreatic cancer research 

and the consequent lack of a stable, 

committed workforce to achieve research 

goals. As a result, the loss of even a small 

fraction of these researchers and research 

projects would seriously undermine an 

already limited research effort. 

The pancreatic cancer research community is 

encouraged by the comprehensive and 

effective way that HIV/AIDS has been 

addressed in America. For this disease, a 

basic scientific and cultural shift resulted in 

important progress. New dollars poured in to 

encourage institutions and investigators to 

Health of the Field and Overarching Issues 7 
create an effective infrastructure and launch 

new research initiatives. As a result, new 

and outstanding projects were developed, 

and public and private partnerships were 

generated to facilitate research, education, 

and patient access to new drugs. 

Consequently, transmission and death rates 

have decreased markedly. 

During the Pancreatic Cancer PRG 

Roundtable, the lack of a critical mass of 

personnel and resources dedicated to 

pancreatic cancer research was often cited. A 

special panel discussion was held on career 

development and funding issues in 

pancreatic cancer research and treatment. 

Overarching issues of resource deployment 

in funding, career development, and training 

were discussed. The paragraphs below both 

summarize the panel discussion and 

synthesize other discussions of these issues 

that occurred in many of the breakout 

sessions. 

Three overarching, high-impact strategies 

were identified to augment pancreatic cancer 

research levels overall and speed progress 

against the disease: 

• Specialized training programs in 

pancreatic cancer research. Training 

new investigators and encouraging 

established investigators to focus on 

pancreatic cancer is essential to increase 

the number of researchers focusing on 

this disease. Although the NCI and NIH 

currently have in place several training 

mechanisms to support career 

development in cancer research, 

specialized training in pancreatic cancer 

research is critical because 

multidisciplinary approaches are 

required at all levels to address the 

disease. For example, multidisciplinary 

collaborations are crucial to progress in 

risk factor determination (involving 

molecular geneticists, physicianscientists, scientists in other disciplines, 

epidemiologists, statisticians, and data 

managers), risk reduction (physicianscientists, patient and public educators, 

epidemiologists, and statisticians), early 

detection (physician scientists in 

gastroenterology, abdominal imaging, 

oncology, biological sciences, physical 

sciences, engineering, and 

epidemiology), and treatment (physicianscientists in clinical oncology specialties, 

gastroenterology, immunology, biology, 

epidemiology, and pharmacology). 

Funding for such training would build on 

the commitment of recipient institutions 

to provide a supportive environment for 

these activities. Given the troubled 

health care environment, however, 

additional incentives may be necessary 

to encourage institutions to make this 

commitment. Encouraging established 

investigators to focus on pancreatic 

cancer will require new competitive 

funding opportunities from the NIH to 

provide some assurance that stable 

support for this research is possible. 

• NIH-based coordinating mechanism 

for pancreatic cancer research 

applications. NCI resources are needed 

to produce the paradigm shift that will 

identify research opportunities and 

encourage new investigators. Increasing 

the number of NIH-funded research 

projects in pancreatic cancer can be 

addressed in a number of ways, but an 

important initial step would be for NCI 

to establish an interdisciplinary 

coordinating mechanism to foster and 

track pancreatic cancer research 

applications and progress. This activity 

would help direct applications to 

appropriate study sections for review, 

foster special funding consideration for 

new investigators, encourage exception 

funding for applications meeting 

8 Pancreatic Cancer: An Agenda for Action 
identified needs, and coordinate 

extramural and intramural initiatives. 

Establishing pancreatic cancer research 

as a high priority will inevitably lead to a 

stronger research base. 

• Centers of excellence for pancreatic 

cancer care and research. Currently, 

only one-third of pancreatic cancer 

patients are referred to institutions that 

treat more than 25 patients per year, or 

that perform more than 25 pancreatic 

resections per year. Research has shown 

that institutions that perform more 

pancreatectomies provide an improved 

level of care with superior outcomes 

compared to centers that perform 

relatively few of these surgeries. Further, 

to achieve optimal research productivity, 

scientists need a sufficiently large cohort 

of patients, excellent access to emerging 

technology, and effective collaborative 

and cooperative relationships. Centers of 

excellence in pancreatic cancer would 

optimize both research and patient 

outcomes and facilitate the diffusion of 

knowledge into the community. These 

centers would offer broad clinical 

expertise, thereby attracting significant 

patient volume, provide state-of-the-art 

diagnosis and treatment, and integrate 

with a core of scientific investigators 

evaluating issues critical to this disease. 

Established models for organ 

transplantation and trauma that have 

improved research and care in those 

fields by concentrating resources and 

developing appropriate infrastructures 

could likewise be used to improve 

opportunities for focused pancreatic 

cancer research. 

Implementing these strategies will produce a 

pancreatic cancer research effort that is more 

robust scientifically, better supported, and 

more effectively organized. Most 

importantly, these changes will produce 

advances that benefit the patients and 

families who are faced with this extremely 

difficult disease. 

Health of the Field and Overarching Issues 9 

II. Research Priorities 
Tumor Biology

STATE OF THE SCIENCE 

Recent scientific advances have created an 

unprecedented opportunity to make 

significant progress in diagnosing and 

treating pancreatic cancer. Discoveries made 

through the Human Genome Project and 

new array technology for DNA, RNA, 

proteins, and tissues have enabled us to 

accomplish multiparametric analyses of gene 

and protein expression on multiple tissue 

samples. 

Genetic alterations identified to date in 

invasive pancreatic cancer include activation 

of the K-ras2 oncogene, overexpression of 

specific growth factors and their associated 

receptors, and inactivation of the p16, p53, 

MADH4, BRCA2, MKK4, STK11, TGFBR1, 

and TGFBR2 tumor suppressor genes and 

certain DNA mismatch-repair genes. These 

genetic alterations are associated with the 

activation of specific transcription factors, 

including relA. 

The advances in our understanding of 

pancreatic cancer biology have a number of 

important implications. They have shed light 

on precursor lesions that give rise to 

infiltrating pancreatic cancer. A number of 

the genetic alterations characteristic of 

invasive pancreatic cancer, including 

activation of the K-ras2 gene and 

inactivation of the p16, p53, DPC4 and 

BRCA2 tumor suppressor genes, have been 

demonstrated in non-invasive epithelial 

proliferations in the pancreatic ducts and 

ductules. These epithelial proliferations, 

called pancreatic intraepithelial neoplasms 

(PanINs) provide an exciting target of 

research on chemoprevention and early 

detection. 

Discovery of genetic alterations important in 

infiltrating pancreatic cancer has advanced 

our understanding of familial pancreatic 

cancer. For example, germline mutations in 

the p16, BRCA2, PRSS1, and STK11 genes 

have been shown to predispose carriers to 

pancreatic cancer. These discoveries provide 

molecular tools for risk assessment and 

provide insight into signaling pathways 

altered in these cancers. By characterizing 

altered signaling pathways, we are 

discovering novel targets for therapy. 

Inactivation of the DPC4 (MADH4, SMAD4) 

tumor suppressor gene in the majority of 

pancreatic cancers disrupts the TGF-$

signaling pathway, suggesting that restoring 

this pathway may be a potential target for 

therapy. 

Infiltrating carcinoma in the pancreas often 

is accompanied by an intense host-stromal 

reaction, and recent advances have markedly 

improved our understanding of host-stromal 

interactions in these neoplasms. For 

example, we now know that infiltrating 

pancreatic carcinoma is characterized by 

aberrant expression of several growth factors 

(epidermal growth factor family, fibroblast 

growth factor, platelet-derived growth factor 

B, TGF-$, insulin-like growth factor-1 and 

nerve growth factor), enhanced angiogenesis 

with increased VEG-F expression, resistance 

to apoptosis, altered epithelial-mesenchymal 

interactions, excessive production of 

proteases including urokinase-like 

plasminogen activator, and an altered 

extracellular matrix. Each advance in our 

understanding of these factors and 

interactions provides a new target for novel 

approaches to diagnose and treat pancreatic 

cancer. 

A unique and heterogeneous disease, 

pancreatic cancer is difficult to study. We 

Research Priorities 11 
have yet to define all of the molecular 

processes that cause or accompany the 

pathogenesis of benign and malignant 

diseases of the pancreas, and we are 

hampered by a poor understanding of the 

molecular aspects of normal cell 

differentiation and development of the gland 

itself. The origin and nature of cells that are 

transformed in pancreatic cancer are not well 

defined. There is great diversity in the 

morphology and biological properties of 

different pancreatic tumors, yet we have 

little understanding of whether these 

differences portend differences in prognosis 

or require distinct treatments. Pancreatic 

tumors display a high degree of resistance to 

conventional chemotherapy and radiation 

therapy. Diagnosis, treatment, and our 

understanding of the disease are complicated 

by the intense desmoplastic reaction 

associated with most pancreatic carcinomas, 

which has not been studied systematically. 

Pancreatic tumors display insidious growth 

properties—they are undetectable at early 

stages and therefore go undiagnosed for long 

periods of time. Because clearly evident 

symptoms of pancreatic cancer are not 

present until the disease is advanced, patient 

survival after diagnosis is short. 

Nonetheless, many new opportunities exist 

for research with considerable potential to 

reduce morbidity and mortality from this 

difficult disease. The promising early results 

of tissue-based gene and protein expression 

analysis in defining tumor biology has 

created a pressing need for specific 

resources such as high quality human 

specimens corresponding to all phases of 

disease, from incipient neoplasia to invasive 

and metastatic disease. At the clinical level, 

uniform reproducible criteria are lacking for 

classifying tumors and non-invasive 

epithelial proliferations that may represent 

precursor lesions. Training and quality 

control guidelines, and reimbursement for 

tissue acquisition, handling, and tracking are 

needed for both pathologists and surgeons. 

In addition, in vitro, ex vivo, and animal 

models are needed that faithfully 

recapitulate the complex biology of invasive 

human pancreatic cancer and its precursors. 

RESEARCH PRIORITIES 

1. Achieve a more complete 

understanding of the normal biology 

of the pancreas. 

New information about pancreatic 

development has led to insights regarding 

nuclear transcription factors and signaling 

pathways regulating pancreatic 

progenitor/precursor cell expansion and 

differentiation. Many of these transcription 

factors (e.g., Pax6) are capable of acting as 

transforming oncogenes when expressed 

abnormally. While most research in 

pancreatic development has been directed 

toward identifying precursor/progenitor cells 

as a potential source for islet cell 

transplantation in diabetes, this research also 

might prove useful in clarifying questions 

regarding the cell(s) of origin, the nature of 

precursor lesions, and cell differentiation 

regulation in pancreatic cancer pathogenesis. 

In fact, notwithstanding established ductal 

differentiation features, the true cell of 

origin for pancreatic ductal adenocarcinoma 

remains unknown. Ductal adenocarcinomas 

may arise from fully differentiated ductal 

epithelium, from other cell lineages (e.g., 

acinar cells) by means of 

transdifferentiation/dedifferentiation, or 

from pluripotent precursor/progenitor cells. 

A more complete understanding of the 

normal pancreas at each stage of 

development is essential for future advances 

in detecting, preventing, and treating 

pancreatic cancer. 

Developmental biology techniques should 

prove useful for investigating cell lineage 

relationships in various animal models of 

12 Pancreatic Cancer: An Agenda for Action 
pancreatic cancer and ultimately, in human 

disease. For example, novel cell labeling 

techniques have been developed for tracing 

cell lineage (i.e., mapping precursor-progeny 

relationships) in vivo during embryonic 

development. Understanding 

precursor/progenitor cell biology has greatly 

aided the development of diagnostic and 

therapeutic tools in leukemias and in cancer 

immunology. It is reasonable to anticipate 

that this knowledge will likewise be 

valuable for improving pancreatic cancer 

prevention, diagnosis, and treatment. 

Therefore, a high priority of research should 

be to isolate, characterize, and propagate 

cells that initially differentiate into the gland 

itself. These cells, or their immediate 

descendants, are likely targets for the various 

agents that cause pancreatic cancer and may 

be potential targets for chemoprevention. 

Recommendations 

• Identify the precursor/progenitor cells of 

the exocrine and endocrine pancreas; 

determine the plasticity (i.e., vertical or 

horizontal differentiation) of cells at 

each step of differentiation, and 

determine the mechanisms by which one 

cell type can differentiate into another. 

• Discover and validate markers of cell 

lineage and phenotype; develop normal 

non-transformed epithelial cell lines for 

all pancreatic cell types. 

• Define the mechanisms of interaction 

between the principal cell types involved 

in pancreas development and in the 

normal adult pancreas (e.g., islet-ductal 

interactions, stromal-epithelial 

interactions). 

• Characterize patterns of gene expression 

in cells involved in pancreas 

development and in the normal adult 

pancreas, and correlate these patterns 

with morphology and differentiation; 

define the molecular control of growth, 

death, and differentiation during normal 

pancreatic development and in the 

normal adult pancreas. 

• Define the range of normal variation in 

anatomy, cell-to-cell interaction, 

biology, and response to injury in the 

adult pancreas over time, from person to 

person, and within the gland. This 

includes the biology of normal ducts, 

including flow rates, concentrations 

(e.g., across ducts, particularly as they 

apply to screening and imaging), and 

turnover rates. 

• Elucidate the relationship between 

progenitor/precursor cells and pancreatic 

neoplasia. 

• Develop, contrast, and correlate animal 

models with human biology in relation 

to the points above. 

2. Elucidate the pathogenesis of 

pancreatic adenocarcinoma. 

Current knowledge of the genetics and 

biology of precursor lesions of pancreatic 

cancer and their progression to invasive, 

metastatic disease is incomplete. Significant 

gaps exist in our understanding of 

predisposition/modifier genes and how the 

fundamental genetic alterations affect 

signaling pathways that control the cell cycle 

and differentiation of ductal epithelial cells; 

how they initiate and induce tumorigenesis, 

tumor invasion, and metastasis; and how 

they generate resistance to chemotherapy 

and radiation. This information is crucial 

given the unique biological and clinical 

characteristics of pancreatic 

adenocarcinoma. 

In addition, genetic changes and expression 

differences must be correlated with cellular, 

Research Priorities 13 
histologic, and clinical phenotypes to 

determine whether there are specific tumor 

subtypes. For example, carcinomas with 

microsatellite instability may differ from 

conventional adenocarcinomas in their 

histologic appearance, prognosis, 

aggressiveness, and response to cytotoxic 

drugs. Clearly identifying pancreatic tumor 

subtypes can be expected to improve drug 

development, intervention selection, and 

prognosis assessment. 

Innate invasive and metastatic potential is a 

distinctive feature of most pancreatic 

adenocarcinomas; metastases to the liver 

almost always develop, even after 

potentially “curative” surgery that reduces 

local recurrence. Little is known about the 

genetic mechanisms and signaling pathways 

responsible for pancreatic cancer metastasis. 

Recommendations 

• Identify the precursor lesions to invasive 

pancreatic carcinoma and define their 

fundamental genetic alterations, patterns 

of gene and protein expression, and 

morphologic phenotypes. This will 

require new modalities to detect and 

monitor pancreatic precursor lesions in 

patients, new sampling methods to 

perform serial samplings in patients with 

potential pancreatic precursor lesions, 

and technologies for genotyping and 

phenotyping small samples from 

formalin-fixed, paraffin-embedded 

tissues. 

• Define the fundamental genetic 

alterations and patterns of gene and 

protein expression in invasive and 

metastatic pancreatic carcinoma, and 

correlate these alterations and patterns 

with morphologic phenotypes and with 

clinical outcome. 

• Determine the cell-cell and cell-matrix 

interactions in precursor lesions, 

invasive, and metastatic cancer, and the 

relationship of these interactions to the 

fundamental genetic alterations, gene 

and protein expression patterns, and 

morphologic phenotypes. 

• Define the biological and clinical 

parameters that predict the risk of 

progression from precursor lesions to 

invasive carcinoma. 

• Define the importance of regional 

variations within the pancreas (field 

effect) and of individual variation, as 

well as the aging process, with respect to 

factors that contribute to pancreatic 

carcinogenesis. 

• Determine the biologic and molecular 

alterations in the tumor-associated nonneoplastic stroma and their roles in 

invasion and metastasis. 

• Correlate findings from the activities 

above with diagnosis, response to 

therapy, outcome, and familial risk. 

3. Study the natural history of the 

pancreatic cancer stroma and 

desmoplasia. 

The origin and functions of the intense 

desmoplastic reaction observed in most 

cases of pancreatic ductal adenocarcinoma is 

a poorly understood area of pancreatic 

cancer pathobiology. A number of complex 

biochemical alterations contribute to this 

reaction and to formation of the resulting 

stroma. Several roles have been 

hypothesized for the stroma in pancreatic 

cancer development and maintenance, but a 

better understanding is needed of the basic 

mechanisms involved in development of the 

stroma, its interaction with pancreatic cancer 

14 Pancreatic Cancer: An Agenda for Action 
cells, and its role in the pathogenesis of 

pancreatic cancer. 

Studies should include evaluations of the 

role of the stroma in normal pancreatic 

tissue, chronic pancreatitis, and pancreatic 

cancer. It is believed that the stroma may 

promote the spread of cancer, block the 

effectiveness of therapy, and interfere with 

immune responses to malignant lesions. To 

assess these possibilities, it is important to 

determine the origin of the desmoplastic 

reaction, and to determine whether cancer 

growth and spread will be arrested if the 

stroma is altered. In addition, the potential of 

stroma to complicate or interfere with 

diagnostic or surveillance procedures should 

be investigated. 

Recommendations 

• Study in detail how tumor-associated 

stroma arises, and whether and how it 

contributes to aberrant mitogenic 

signaling. 

• Investigate molecular interactions 

between stroma and tumor cells, 

especially concerning the role of the 

stroma in pancreatic cancer invasion and 

metastasis, and how the stroma-derived 

growth advantage of cancer cells can be 

reduced or eliminated. 

• Characterize the cellular and 

biochemical microenvironment of 

stroma, including detailed analysis of (1) 

the cellular components of the stroma, 

(2) the extracellular matrix, interstitium, 

and basement membrane (including 

collagen types and proteoglycan 

composition), and (3) the various growth 

factors that mediate stroma growth and 

its interactions with pancreatic cancer. 

4. Investigate clinically important hosttumor interactions and develop novel 

therapeutic strategies to address them. 

Understanding host-tumor interactions is 

critical to understanding basic biologic 

principles about pancreatic cancer 

development and progression. These 

interactions also may offer novel strategies 

for therapeutic intervention and must be 

considered when developing and testing new 

therapeutic interventions for this disease. 

Studies aimed at understanding the immune 

system’s role in controlling tumor 

progression, and the role that angiogenesis 

and apoptosis mechanisms play in pancreatic 

tumor development, progression, and 

metastasis are underrepresented in the 

literature. Even less emphasis has been 

directed toward understanding the 

mechanisms by which pancreatic cancer 

induces constitutional symptoms such as 

cachexia, a problem that appears to 

contribute significantly to the rapid demise 

of patients with this disease. Investigating 

these research areas offers opportunities to 

define new targets for treatment and control 

of pancreatic cancer, and for improved 

patient performance status and quality of 

life. 

It is well established that tumor proteins can 

be processed and presented to immune cells, 

evoking an immune response, and it is 

reasonable to believe that it is possible to 

activate the immune system specifically to 

recognize pancreatic tumor cells. The 

detection of tumor-specific T cells and 

antibodies in cancer patients provides 

additional evidence that the immune system 

is important in controlling cancer. However, 

pancreatic tumors may evade immune 

recognition by altering expression of critical 

tumor rejection antigens or by employing 

mechanisms of peripheral immune tolerance 

or general immune suppression. Despite 

these factors, early clinical trials testing a 

Research Priorities 15 
variety of vaccine approaches in pancreatic 

cancer patients have demonstrated tumorspecific immune response augmentation. 

Thus, vaccines that target pancreatic tumor 

antigens may find a role in treating minimal 

residual disease and/or in primary 

prevention. 

Progress in stimulating immune responses 

against pancreatic cancer would be 

accelerated by developing and testing novel 

vaccine approaches for this disease. This 

research would be facilitated by appropriate 

preclinical models that would allow more 

stringent screening of new vaccine 

approaches (e.g., transgenic mouse models 

that express or lose expression of genes 

known to be important in human pancreatic 

tumor development and progression, and 

that develop pancreatic tumors) and vaccine 

approaches employed early in cancer 

development to evaluate strategies for 

primary prevention. Vaccine approaches also 

would be aided by the identification of new 

pancreatic tumor-specific immune targets. 

Angiogenesis is believed to be necessary for 

cancer development, growth, invasion, and 

metastasis, and inhibition of angiogenesis is 

postulated to be an effective therapeutic 

strategy. This approach to therapy may be 

particularly attractive for pancreatic cancers, 

because the malignant cells have proven 

refractory to available cytotoxic therapies. 

However, there exists both a lack of 

understanding of angiogenesis and concern 

that antiangiogenic therapy will not be 

effective against the mature vessels that 

exist in pancreatic cancer or against 

metastases to highly vascularized sites such 

as the liver. Study of the development and 

function of tumor vasculature in pancreatic 

cancer specimens and evaluation of the 

effects of angiogenesis inhibitors in animal 

tumor models that more closely resemble 

human pancreatic cancer (e.g., models that 

reproduce the substantial time course and 

stromal reaction of human pancreatic 

tumors) may facilitate evaluation of this 

approach to therapy. 

Ultimately, antiangiogenesis strategies and 

agents will need to be tested in clinical trials, 

and informative clinical trials should be 

considered earlier rather than later in this 

disease. Research also is needed to define 

relevant therapeutic endpoints in addition to 

known clinical endpoints to validate noninvasive monitoring and imaging techniques 

(e.g., PET, MRI). 

In tumors such as pancreatic carcinoma, 

chemotherapy and radiotherapy resistance 

are associated with mechanisms that inhibit 

apoptosis. Genetic alterations identified thus 

far in pancreatic tumor development and 

progression (e.g., K-ras2 mutation, p53 

inactivation, NF-6B activation) are known to 

play a role in inhibiting apoptosis. One 

research priority should be to define cellular 

pathways of apoptosis induction and 

inhibition, and the interaction of these 

pathways to produce apoptosis resistance in 

pancreatic cancer. Discovering ways to 

modulate these pathways or their interaction 

also is important so that apoptosis of 

pancreatic cancer cells can be effectively 

induced by available cytotoxic agents or 

radiation. Understanding the actions and 

therapeutic potential of apoptosis-inducing 

agents would be facilitated by study in 

appropriate animal models. In addition, noninvasive methods for studying apoptosis in 

vivo are urgently needed. Clinical trials of 

agents targeting apoptosis should include 

markers of apoptosis as surrogate endpoints 

to better understand the mechanisms by 

which new antitumor agents either succeed 

or fail. 

Pancreatic cancer patients suffer more than 

most other cancer patients from cancerrelated constitutional problems such as 

cachexia, weight loss, fatigue, and 

16 Pancreatic Cancer: An Agenda for Action 
depression. These symptoms and signs 

decrease a patient’s performance status and 

both quality and quantity of life, and are 

thought to adversely affect a patient’s ability 

to respond to therapies. The mechanisms 

associated with cancer-related sequelae are 

not well understood, but recent evidence 

indicates that tumor-derived factors such as 

zinc alpha2 glycoprotein and a proteolysisinducing factor may contribute to these 

symptoms. Clinical trials testing the actions 

eicosapentaenoic acid (EPA), an inhibitor of 

this signaling pathway, are underway in 

Europe. However, this area of pancreatic 

cancer research is significantly understudied. 

Therefore, another priority is to identify 

additional modulators of pancreatic cancer 

cachexia and the signaling and metabolic 

pathways by which they produce their 

effects. These discoveries would provide 

new targets for modulating pancreatic 

cancer-associated sequelae, and agents 

developed for this purpose should be rapidly 

incorporated into clinical trials testing novel 

anticancer agents. Improved performance 

status may extend patients’ lifespan and 

ability to respond to other therapies. 

Recommendations 

• Investigate clinically important hosttumor interactions, including modulators 

and pathways that mediate tumor 

immunity, resistance to chemo- and 

radiation therapy, cachexia, and other 

factors that affect quality of life and 

longevity. 

• Investigate and develop novel 

therapeutic strategies that circumvent 

resistance to apoptosis and immune 

attack and modulate secondary effects of 

tumors on local and distant organs that 

decrease patient survival. 

RESOURCES NEEDED 

1. Create specimen banks of normal and 

neoplastic human pancreatic tissue. 

To pursue these research priorities, 

investigators need easy access to high 

quality tissue from normal pancreas, 

precursor lesions, and invasive and 

metastatic tumors. These specimens must be 

collected and stored according to 

standardized procedures. They should be 

available through an easily accessible 

repository, with accompanying clinical and 

epidemiologic data. This resource can be 

used for DNA analysis, to develop a 

database of gene and protein expression 

profiles, comparative genomic hybridization, 

and analysis of mutations in key genes that 

contribute to the pathogenesis of the disease. 

(See also Section III, Scientific Toolkit.) 

2. Develop experimental model systems. 

Also needed to pursue these priorities are in 

vitro, ex vivo, and animal models that 

faithfully recapitulate the complex biology 

of invasive human pancreatic cancer and its 

precursors. No existing animal model meets 

this criterion, and the dozens of human 

pancreatic cell lines that have been isolated 

remain underutilized for this purpose. 

Particular emphasis should be given to 

developing mouse and other models of 

normal and aberrant development, precursor 

lesions, signal transduction pathways, gene 

expression, carcinogenesis, and interactions 

between the tumor, stroma, and host. (See 

also Section III, Scientific Toolkit.) 

Research Priorities 17 
Risk, Prevention, Screening, and Diagnosis

STATE OF THE SCIENCE 

Pancreatic cancer is the fifth leading cause 

of cancer death in the United States. 

Unfortunately, the vast majority of patients 

present with non-specific symptoms and do 

not exhibit specific symptoms until the 

disease is advanced. Pancreatic cancer also 

metastasizes rapidly —many primary tumors 

that are less than 1–2 cm in size have spread 

beyond the pancreas. Consequently, 

identifying premalignant lesions and highrisk candidates for prevention are important 

goals, and determining genetic and 

environmental risk factors and geneenvironment interactions are critical to 

achieving these goals. 

Risk 

Pancreatic cancer is a rapidly fatal disease. 

Median age at diagnosis is 71 years, and 

incidence varies by race, gender, and 

geography. The disease occurs more often in 

African Americans than in whites and in 

men more than in women; incidence rates 

around the world vary approximately 30-

fold. 

In addition to aging, there are four probable 

risk factors for pancreatic cancer: family 

history, cigarette smoking, long-standing 

diabetes, and hereditary and chronic 

pancreatitis. 

Family history—People in affected families 

have about a three-fold higher risk compared 

with the general population. At least five 

percent of patients with pancreatic cancer 

report a family history of the disease. 

Hereditary syndromes, such as familial 

atypical multiple mole melanoma 

(FAMMM) syndrome, familial breast 

cancer, Peutz-Jeghers syndrome, inherited 

mismatch repair deficiencies, and hereditary 

pancreatitis account for only a small percent 

of all pancreatic cancer cases. Some genes 

associated with these syndromes have been 

identified and include p16, BRCA2, 

STK11/LKB1, hMSH2, hMLH1, and PRSS1 

(cationic trypsinogen). 

Cigarette smoking—Smoking is believed 

to cause about one quarter to one third of 

pancreatic cancers. People who smoke for 

twenty years or more have double the risk of 

those who have never smoked, and recent 

evidence indicates that this risk may be even 

higher when certain genetic polymorphisms 

are present. 

Long-standing diabetes—There is a twofold increased risk of pancreatic cancer 

among people who were diagnosed with 

diabetes mellitus at least five years before 

their diagnosis of pancreatic cancer. This 

observation suggests that diabetes may be an 

independent risk factor for pancreatic 

cancer, as well as a possible consequence of 

the disease. The mechanism involved, 

however, is unclear. 

Chronic pancreatitis—Pancreatic cancer 

risk among individuals with hereditary 

pancreatitis or non-hereditary chronic 

pancreatitis is about 50 times and 16 to 20 

times higher, respectively, than those 

without chronic pancreatitis. 

Studies also have implicated a number of 

other factors, including diet and nutrition, 

heavy alcohol consumption, and certain 

occupational exposures, but these findings 

have been inconsistent. 

Diet and nutrition—Increased pancreatic 

cancer risk has been associated with high 

intake of meat, fat, and carbohydrates, and 

18 Pancreatic Cancer: An Agenda for Action 
with elevated body mass index and caloric 

intake. An NCI study found an interaction 

between body mass index and caloric intake, 

suggesting that caloric intake in excess of 

that required to maintain energy balance may 

increase risk. 

Alcohol—Alcohol consumption at the level 

typically consumed by the U.S. population 

does not appear to increase risk; however, 

approximately ten studies have reported an 

increased risk associated with heavy alcohol 

consumption. 

Occupational exposures—Organochlorine 

compounds (DDT, DDE, and PCBs) have 

been associated with elevated risk in a small 

number of studies. Dry cleaning workers 

have an increased risk of pancreatic cancer, 

possibly due to exposure to chlorinated 

hydrocarbon solvents. 

Prevention 

Smoking cessation appears to reduce 

pancreatic cancer risk. A few recent studies 

suggest that risk may revert to the level of 

nonsmokers after long-term cessation. 

Fruit and vegetable intake may have a 

protective effect against pancreatic cancer. 

The effect appears to be stronger for 

vegetables, particularly cruciferous 

vegetables. 

Screening and Diagnosis 

A number of formidable obstacles limit the 

ability of health care providers to screen atrisk individuals for early neoplastic changes 

and to make a very early and specific 

diagnosis of pancreatic cancer. Although 

radiologic techniques such as computerized 

tomographic (CT) scanning, magnetic 

resonance imaging (MRI), endoscopic 

retrograde cholangiopancreatography 

(ERCP) and endoscopic ultrasonography 

(EUS) provide high resolution images of 

small lesions, pancreatic cancers have 

almost always spread beyond the gland by 

the time of detection. Known biological 

markers are less sensitive than imaging 

techniques, and they lack specificity. Better 

screening and diagnostic techniques are 

urgently needed. 

RESEARCH PRIORITIES 

1. Identify genetic and environmental 

factors and gene-environment 

interactions that contribute to 

pancreatic cancer development. 

Identifying factors that increase pancreatic 

cancer risk in humans is critical, not only to 

understand causes of the disease, but to 

improve its prevention, detection, and 

treatment. Until these factors are identified, 

progress in developing and implementing 

preventive strategies, screening protocols, 

early detection technologies, and more 

effective therapies remains difficult. 

Intensive research effort has led to the 

discovery of a number of rare genes and 

environmental factors that contribute to 

human pancreatic cancer. However, more 

common genes, genetic polymorphisms, and 

specific risk factors have yet to be identified, 

and gene-environment interactions must be 

investigated to understand their significance. 

Many barriers have limited progress in 

identifying pancreatic cancer genes and risk 

factors. The lack of early disease markers, 

the late onset of disease-specific symptoms, 

the shortage of high quality biological 

samples from affected and linked family 

members, and the limited number of 

pancreatic cancer families included in 

research protocols hinder efforts to pinpoint 

pancreatic cancer genes by linkage analysis. 

Thus, many of the genetic defects underlying 

familial pancreatic cancer and hereditary 

pancreatitis still are unknown. 

Research Priorities 19 
Because pancreatic cancer is a rapidly fatal 

disease, many epidemiologic studies have 

relied principally on data from next of kin. 

As has been documented in a number of 

studies, next of kin provide less accurate 

information than patients, particularly with 

regard to detailed exposure data. Such 

misclassification of exposure leads to biased 

estimates of risk, potentially contributing to 

the inconsistency of findings across casecontrol studies conducted to date. However, 

because of the rapid deterioration in the 

condition of pancreatic cancer patients, the 

possibility of recall bias from ill patients is a 

concern, though its magnitude is not known. 

Additional complications in epidemiologic 

studies are the paucity of exposure markers 

(e.g., organochlorines) and the long latent 

period of pancreatic cancer, which makes it 

difficult to identify the timing of exposures 

to carcinogens. 

Obtaining appropriate biological specimens 

continues to be a critical problem for 

investigations of genetic and environmental 

factors, and gene-environment interactions. 

Obstacles include the lack of cooperation 

between investigators and various health 

care providers, and questions about optimal 

specimens for studying risk (e.g., biopsy, 

surgical tissue, pancreatic juice, blood, 

serum, stool) and how to obtain them. The 

absence of samples readily available for high 

volume/high throughput analyses in 

epidemiologic studies has limited the 

potential impact of such laboratory 

correlative studies. In addition, the rapidly 

fatal nature of the disease and the small 

number of patients that normally are accrued 

in any one geographic area make cooperative 

studies and data pooling essential to 

progress. 

Finally, current animal models for pancreatic 

cancer research are inadequate, and animal 

models for hereditary pancreatitis are 

lacking. 

Recommendations 

• Facilitate the development of 

interdisciplinary case-control studies that 

will provide adequate sample size for 

accurately defining pancreatic cancer 

risk factors. These should be large, 

multicenter studies that include ultrarapid case ascertainment, in-person 

patient interviews, and comprehensive 

biospecimen collection. 

• Further delineate the genetic basis of 

familial pancreatic cancer and hereditary 

pancreatitis. Because of the limited size 

of most familial pancreatic cancer 

kindreds, wide geographic dispersion of 

family members, and heterogeneity of 

phenotypes, cooperative studies and 

consortia are recommended. 

• Evaluate environmental risk factors and 

gene-environment interactions in 

appropriate animal models. Clinical and 

laboratory studies are needed, and 

appropriate animal models must be 

developed to accomplish the latter. 

2. Develop, implement, and evaluate 

approaches to prevent pancreatic 

cancer in high- risk cohorts (e.g., 

familial pancreatic cancer, hereditary 

pancreatitis). Studies should be 

performed in both humans and 

animal models of early neoplasia (e.g., 

pancreatic intraepithelial neoplasia, or 

PanIN-3). 

Pancreatic cancer usually is identified after 

the tumor has metastasized beyond the 

pancreas, and treatment is relatively 

ineffective. When mutations and 

polymorphisms that predispose to pancreatic 

cancer are identified and environmental risk 

factors are determined, prevention of 

pancreatic cancer in high-risk groups may 

20 Pancreatic Cancer: An Agenda for Action 
become possible. Currently, the ability to 

consider preventive strategies is limited. 

Recommendations 

• Develop and test risk reduction strategies 

in high-risk populations (e.g., smoking 

cessation, reduced alcohol consumption, 

dietary changes). 

• Develop chemoprevention trials using 

agents that have proven effective in other 

malignancies or that target pathways 

critical to neoplastic transformation and 

progression. 

• Develop vaccines focused on immune 

responses targeted to pre-invasive 

neoplastic epithelium (PanIN-3). 

3. Identify and develop surveillance and 

diagnosis methods for early detection 

of pancreatic cancer and its 

precursors. 

Several major barriers to surveillance and 

diagnosis in pancreatic cancer have been 

identified. For example, no effective 

screening protocols are available for any 

high-risk cohort, and markers—both current 

serum tumor markers and molecular markers 

ascertained in pancreatic duct aspirates—are 

insensitive and nonspecific. Further, 

detection with available imaging modalities 

is challenging in a disease characterized by 

metastatic tumor spread even when the 

primary tumor is very small. Imaging with 

CT, MR, ECRP, and EUS is not specific for 

pancreatic cancer in the presence of other 

pancreatic pathology (e.g., chronic 

pancreatitis, mucinous cystadenoma, and 

intraductal papillary mucinous neoplasm). 

The rapid fatality of the disease also makes 

it difficult to follow cohort study 

participants long enough to determine the 

efficacy of screening modalities, making 

cooperative efforts and consortia essential to 

progress. In addition, the five-year 

timeframe for NCI grants is inadequate to 

complete many types of studies. Longerterm arrangements are needed for sufficient 

collection of specimens, clinical 

information, and natural history data to test 

the value of tumor markers and to assess 

imaging modalities. Finally, a major barrier 

to pancreatic cancer research has been the 

lack of a well structured biospecimen 

repository containing specimens that have 

been well annotated (e.g., information on 

patient demographics, exposure, family 

history, clinical course) and for which 

patients have given full informed consent for 

their present and future use. 

Recommendations 

• Delineate and validate effective 

molecular biomarkers of pre-invasive 

and invasive disease using a variety of 

banked specimens (blood, serum, 

pancreatic juice, stool, tissue, other body 

fluids) in combination with clinical and 

natural history data. 

• Develop tumor-specific imaging such as 

molecular-targeted imaging; refine stateof-the-art imaging (including CT, MR, 

ERCP, and EUS) with emphasis on 

detecting small invasive and preinvasive lesions in both normal pancreas 

and abnormal pancreas (e.g., chronic 

pancreatitis, mucinous cystadenoma, and 

intraductal papillary mucinous 

neoplasm). This will require 

collaborative research and training that 

provides an interface between molecular 

biology, pathology, and imaging 

technology. New technology such as in 

vivo MR microscopy should be 

evaluated in animal models or explanted 

specimens of invasive and pre-invasive 

neoplasia. 

Research Priorities 21 
• Develop and test screening and 

surveillance protocols in patients from 

familial pancreatic cancer kindreds, 

patients with hereditary pancreatitis, and 

patients with intraductal papillary 

mucinous neoplasm or cystadenoma. 

This will require specimen collection 

and surveillance by state-of-the-art 

imaging conducted at regular intervals. 

Analyses of specimens for biological and 

molecular markers should be correlated 

with imaging and patient outcome. 

RESOURCES NEEDED 

1. Create new registries and expand 

existing registries to identify high-risk 

patients and kindreds (familial 

pancreatic cancer, hereditary 

pancreatitis, and others) for linkage 

analysis, as a tissue and specimen 

resource, to identify screening and 

surveillance cohorts, and for 

epidemiologic assessment of geneenvironment interactions. 

2. Develop specimen banks for all types 

of biomaterials—blood, serum, 

pancreatic juice, stool, tumors, other 

body fluids—to redress the paucity of 

specimens available for analysis. (See 

Scientific Toolkit.) 

3. Establish consortia of large, aging 

cohorts for pooled analyses to 

elucidate causal factors for pancreatic 

cancer. In many existing cohort studies, 

participants generally are too young to 

provide an adequate number of 

pancreatic patients for assessing risk 

factors and the efficacy of screening 

modalities. 

4. Develop education and training 

resources for investigators and health 

care providers about pancreatic 

cancer risk assessment, evaluation 

protocols, and sample collection. The 

current lack of knowledge and 

understanding about these central issues 

greatly limits the likelihood of making 

significant progress in pancreatic cancer 

research. 

5. Develop a high quality, high 

resolution, Web-based imaging library 

to be used as an educational tool for 

health care providers, a research tool 

for the scientific community, a 

reference standard for imaging 

studies, and a source of images for 

application of artificial intelligence 

and other post-imaging processing. 

Epidemiological data can be attached to 

the images for additional research utility. 

6. Establish technology centers for 

comprehensively assessing gene and 

protein expression to facilitate 

identification and evaluation of 

biomarkers for pancreatic cancer and 

its precursors, especially carcinoma in 

situ. 

7. Develop animal models for pancreatic 

cancer, pre-invasive neoplastic lesions, 

and hereditary pancreatitis to be used 

for studies of environmental risk 

factors, gene-environment 

interactions, chemoprevention, 

chemotherapy, radiation therapy, 

vaccines, and imaging. (See Scientific 

Toolkit.) 

22 Pancreatic Cancer: An Agenda for Action 
Therapy

STATE OF THE SCIENCE 

While survival has improved for patients 

with most other gastrointestinal cancers, the 

five-year survival of patients with pancreatic 

adenocarcinoma remains less than five 

percent. Nominal therapeutic advances have 

been made in recent years. The small 

percentage of patients who are candidates 

for resection can undergo surgery with the 

expectation that post-operative mortality and 

morbidity can be minimized, especially at 

experienced centers. A new drug, 

gemcitabine, has improved the quality of life 

and modestly affected the survival of 

patients with locally advanced or metastatic 

pancreatic cancer. Despite these approaches, 

however, the overall impact of therapy for 

pancreatic cancer is quite limited. 

Basic research efforts over the past few 

years have shown that pancreatic 

adenocarcinomas, like other major human 

neoplasms, result from accumulating genetic 

lesions that lead to tumor development and 

promote progression. Though a number of 

these germline and somatic tumor-associated 

alterations have been identified, significant 

gaps exist in our understanding of how these 

alterations initiate the process of pancreatic 

carcinogenesis, how the proteins they 

encode (or fail to encode) interact in 

complex signaling cascades, and how the 

altered intracellular responses mediated by 

abnormal cellular biochemistry interact with 

normal host stromal cells and the immune 

system. In particular, it remains a challenge 

to better understand and determine how the 

genetics and molecular biology of pancreatic 

cancer can be harnessed for therapeutic gain. 

Given the highly aggressive clinical 

characteristics and lack of effective therapies 

for pancreatic cancer, advancing our 

knowledge in these areas is of special 

urgency. 

RESEARCH PRIORITIES 

1. Facilitate the discovery and 

development of targeted therapeutics. 

It is likely that specific signaling pathways 

within tumor cells and between tumor cells, 

stroma (fibroblasts and endothelium), and 

the immune system are altered in pancreatic 

adenocarcinoma and that once identified, 

these pathways can be targeted for 

therapeutic benefit. With this information, it 

should be possible to identify specific 

protein targets that are critical to pancreatic 

cancer growth, metastasis, drug and 

radiation resistance and design 

pharmacologic strategies to interact with 

these critical pathways. 

Growing knowledge of the molecular 

biology of pancreatic cancer should be used 

to identify both existing agents that target 

biologic pathways already known to be 

critical to pancreatic cancer tumorigenesis 

and those that can be identified from new 

insights into key signaling pathways. It also 

is likely that substantial benefit can be 

gained by enhancing standard cytotoxic 

therapy with new targeted therapeutics. 

Recommendations 

• Identify strategies that target specific 

pathways currently understood to be 

important in pancreatic tumorigenesis 

and maintenance, including host-tumor 

interactions such as tumor immunity, 

angiogenesis, and growth factor 

receptors or interactions. 

Research Priorities 23 
• Identify strategies that target specific 

biochemical signaling pathways 

identified from new insights into signal 

transduction pathways. 

• Identify strategies that target specific 

biochemical signaling pathways and 

consequently enhance conventional 

cytotoxic chemotherapy and radiation 

therapy. 

2. Facilitate development of preclinical 

and minimally invasive clinical 

techniques to assess targeted 

therapeutics. 

Discovery and development of novel 

targeted therapeutic strategies with a high 

probability of success in treating pancreatic 

cancer will be facilitated by developing 

relevant preclinical models. These models 

are needed to validate that a specific 

therapeutic agent is capable of affecting its 

target and to assess the impact of that 

intervention on tumor growth and 

metastasis. 

To develop novel targeted therapeutic 

strategies in the clinic, it will be necessary to 

obtain and analyze tumor and host tissues 

for evidence that the target has been 

affected. This important effort will require 

(1) minimally invasive surgical and nonsurgical techniques for obtaining tumor 

tissue serially from patients, and (2) noninvasive imaging techniques that will 

provide both functional (e.g., 

antiangiogenesis, immune-mediated 

mechanisms) and molecular (e.g., apoptosis, 

inhibition of specific signaling pathways) 

data sufficient to determine the effect of the 

targeted therapeutic strategies on the defined 

signaling pathways. It will be necessary to 

validate these non-invasive techniques 

against specific tissue-based assays. 

Recommendations 

• Develop and validate animal models that 

recapitulate the molecular pathogenesis 

of pancreatic cancer for use in testing 

targeted preventive and therapeutic 

strategies (See also Scientific Toolkit). 

• Develop and validate methods (tissuebased and non-invasive) to assess the 

effects of targeted therapeutics in 

patients. 

3. Accelerate research into the 

supportive care of patients with 

pancreatic cancer. 

Patients with pancreatic cancer are affected 

by profound physiologic changes. These 

changes include severe cachexia, asthenia, 

and pain, which are experienced by at least 

85 percent of patients with pancreatic 

adenocarcinoma. 

Emerging data support the hypothesis that 

many patients with pancreatic cancer die due 

to the associated wasting. Cachexia is likely 

to be mediated by specific cytokines and 

other proteins that are produced by 

pancreatic cancer cells, stroma, and immune 

cells. Understanding the biology of cachexia 

may allow us to develop pharmacologic and 

other means to reverse wasting, and this 

should improve quality of life, the ability of 

patients to tolerate anti-cancer therapies, and 

survival. The role of nutrition in mitigating 

this morbidity should be explored. 

Additionally, severe visceral pain is often 

associated with pancreatic cancer. While 

pancreatic cancer pain syndromes often are 

treated with potent narcotic analgesics, nerve 

blocks, or radiation therapy, these 

approaches have side effects, and nerve 

blocks often are not available or ineffective. 

Data also suggest that simply controlling the 

pain associated with pancreatic cancer 

24 Pancreatic Cancer: An Agenda for Action 
translates into improved survival. Therefore, 

innovative approaches to pain management 

are critical to optimize the supportive care of 

pancreatic cancer patients. 

Recommendations 

• Develop interventions to reverse patient 

cachexia and asthenia. 

• Develop improved interventions to 

manage pain associated with pancreatic 

cancer. 

RESOURCES NEEDED 

1. Develop mechanisms to facilitate 

investigator access to novel targeted 

therapeutic agents for preclinical 

studies and clinical trials. 

NCI should develop or facilitate 

mechanisms to speed development of new 

agents. Both industry and academia are 

developing a substantial number of new 

therapeutic agents; however, the broader 

scientific community often does not have 

access to these agents for preclinical and 

clinical studies. In addition, many of these 

agents are not evaluated for the treatment of 

pancreatic cancer as this disease is less 

common than others. These and other 

proprietary concerns also limit the use of 

these agents in combination, especially when 

multiple pharmaceutical companies are 

involved. As a result of these issues, it has 

been difficult to develop and test new agents 

for treating pancreatic cancer. The 

development process could be facilitated 

enormously by broad master agreements 

with the pharmaceutical industry and 

academia that assure access to these 

investigational agents by the research 

community and protect the interests of all 

parties. 

In addition, greater 

clarification/simplification of Food and 

Drug Administration (FDA) and Office of 

Human Research Protection (OHRP) 

regulations is needed. Currently, regulatory 

discussions affecting new drug development 

are conducted only on a case-by-case basis. 

A lack of uniform requirements can create 

confusion and disincentives for development 

of new agents targeting pancreatic cancer, 

particularly with respect to trial design and 

endpoints specific to this disease. Guidelines 

addressing development of therapeutics for 

pancreatic cancer would be useful. 

2. Develop infrastructure for molecular 

target assessment. 

As we develop and test new targeted 

therapeutics, appropriate technology will 

need to be in place for safe serial tissue 

acquisition, including standardized protocols 

for handling the specimens. In addition, noninvasive functional and molecular imaging 

technology must be available for preclinical 

and clinical studies (See also Scientific 

Toolkit). 

3. Improve infrastructure for clinical 

trials and promote patient 

participation. 

• Increase multidisciplinary clinical trials 

and expand the clinical trials network. 

The existing oncology clinical trials 

cooperative group system, including the 

GI Intergroup, develops and conducts 

therapeutically-oriented clinical trials. 

However, professionals of several types 

are not well integrated into the clinical 

trial structure; these include 

gastroenterologists, general surgeons, 

primary care physicians, basic scientists, 

epidemiologists, and others. Optimal 

translation of biological insights to 

clinical use, and of clinical observations 

to laboratory investigation, requires a 

Research Priorities 25 
network that will integrate the relevant 

researchers in real time. Ideally, 

subsequent integration of successful 

strategies developed by these researchers 

with the clinical research trialists 

currently supported by NCI (e.g., Phase 

I, Phase II, cooperative groups, 

Community Clinical Oncology 

Programs) is desired. 

An expanded clinical trials network 

should facilitate pancreatic cancerspecific investigations of high-risk 

cohorts, early diagnosis and treatment; 

coordinate storage of serum, tissue, or 

tumor samples; and develop 

standardized methods for tissue 

handling, processing, storage, and 

sharing. Theoretically, this could be 

accomplished by cooperation between 

two or several centers of excellence for 

pancreatic cancer research. 

• Provide adequate support for 

performance of clinical trials. Funding 

has been inadequate to cover the costs of 

performing therapeutic clinical trials. 

Additional support is needed for 

professionals involved in clinical 

research, including physicians, research 

nurses, statisticians, and clinical trial 

coordinators. Moreover, little support 

exists for the efforts of pathologists, 

radiologists, and other professionals 

collaborating within the current 

structure. Without substantial support for 

this part of the infrastructure, it will be 

impossible to collect samples and 

perform the crucial basic science and 

correlative studies critical for progress; 

these activities entail additional 

procedures and related costs that must be 

supported by the research budget. 

• Optimize clinical trial design specific to 

pancreatic cancer. 

— Explore alternative trial designs to 

address (1) the difficulty of assessing 

response or benefit in patients with 

locally advanced and metastatic 

pancreatic cancer, and (2) the activity 

of new therapeutic strategies that 

may not kill tumor cells, but stop 

their growth. 

— Validate novel surrogate endpoints, 

including disease stabilization, 

biochemical markers, and results of 

functional imaging studies. 

— Develop simple, reliable, and valid 

instruments for assessing clinical 

benefit in pancreatic cancer patients. 

• Develop a dedicated Web site and/or 

other mechanisms for disseminating 

information on pancreatic cancer and 

clinical trials. Research shows that 

patient outcome is improved for patients 

who participate in clinical trials. 

Therefore, all patients with pancreatic 

cancer should be made aware of clinical 

trials as a treatment option. 

26 Pancreatic Cancer: An Agenda for Action 
Health Services Research

STATE OF THE SCIENCE 

Traditionally, health services research 

methods have focused on economic profiles, 

social and behavioral studies, and outcome 

assessments. Health services research that 

specifically addresses pancreatic cancer has 

yet to be fully explored as a field of study; in 

fact, very little health services research has 

focused on this disease. For example, NCI 

has an extensive general health services 

research program, but supports little research 

that is specific to pancreatic cancer. 

In contrast to other cancers, such as 

colorectal or breast cancer, the state of 

pancreatic cancer diagnosis and treatment is 

such that messages about the need for early 

diagnosis are not yet useful, since costeffective tools for population-based 

screening do not yet exist. Instead, resources 

are needed for health services research that 

focuses on post-diagnosis communication. 

Health services research is crucial in 

pancreatic cancer to help ensure that 

patients, families, and health care providers 

are well informed about all aspects of the 

disease. NCI’s recent enhanced commitment 

to cancer communication initiatives provides 

new opportunities for health services 

research relative to pancreatic cancer. 

Advances in tumor biology, diagnosis, and 

treatment can be expected to promote more 

positive attitudes toward pancreatic cancer 

and assist in fulfilling the priorities stated in 

this section. 

RESEARCH PRIORITIES 

1. Identify effective forms of health care 

provider communication with 

pancreatic cancer patients. 

Health care providers treating pancreatic 

cancer patients must know and communicate 

to their patients the availability and value of 

clinical trials, treatment options, pre- and 

post-surgical therapies, and symptom 

management. They should be able to help 

facilitate patient decision making after 

diagnosis, and encourage research 

participation by high-risk families. Health 

care providers also should discuss quality of 

life and end of life issues with their patients, 

and provide current information and/or 

referrals when necessary. The unique needs 

of older patients and older caregivers are of 

special concern. 

Previous studies of health care providerpatient communication have revealed that 

when the provider’s communication is 

compassionate and accurate, the patient is 

more accepting of the messages, thus 

strengthening the health care providerpatient relationship. 

Recommendations 

• Conduct studies of health care providerpatient communication practices, 

patterns, and outcomes in academic and 

community health care systems. 

• Conduct studies to determine which 

health care providers (e.g., physicians, 

nurses, information liaisons, clinical 

research assistants, physician assistants) 

can perform key information 

dissemination tasks in the most efficient 

and effective manner. This initiative 

Research Priorities 27 
should include studies to identify the 

most effective forms of provider 

communication. 

2. Identify determinants of message 

effectiveness in aiding decision 

making by patients. 

Patient decision making is a fundamental 

step in delivering medical care. Very limited 

information is available for understanding 

and predicting how patients make decisions 

or what environments promote optimal 

decision making, especially following a 

pancreatic cancer diagnosis. Patients must 

be made aware of their options—whether by 

a physician, nurse, or other health care 

professional—following a pancreatic cancer 

diagnosis and through the entire course of 

treatment. They also must understand how 

the medical infrastructure works, including 

information on different health care settings 

(e.g., academic medical center, clinical 

center, community hospital), insurance 

issues, and how to get a second opinion. 

The short survival time of pancreatic cancer 

patients forces them to make rapid decisions 

under incredible pressure and stress. A 

number of studies have demonstrated the 

significant influence of family members and 

companions on patient decision making. A 

better understanding is needed of the 

influence of personal networks on the 

decisions made by patients with pancreatic 

cancer. In addition, studies of patient 

comprehension and understanding of 

messages have revealed that both linguistic 

and paralinguistic variables are involved in 

information retention and utilization. 

However, it is not known how these 

variables influence decision making when 

time frames are short. 

The Internet now allows many patients to 

access information quickly and easily, but all 

of this information is not of equal quality or 

usefulness. Patients must be helped to 

understand that these quality differences 

exist and learn to evaluate Internet (and 

other) information effectively. This is 

particularly important for patients with 

pancreatic cancer; because of the high 

mortality rate and short survival time 

associated with the disease, these patients 

may be particularly vulnerable to claims 

about the efficacy of unproven therapies they 

learn of through anecdotal reports. It also 

must be recognized that although Internet 

use continues to expand, a large percentage 

of the pancreatic cancer patient population, 

particularly the medically underserved, do 

not have access to this resource. 

Recommendations 

• Conduct studies of pancreatic cancer 

patients/caregivers to determine how 

information acquisition, retention, and 

comprehension relate to decision 

making. These studies should address 

the types and sources of information 

used (Internet and non-Internet based). 

• Develop communication toolkits for 

patients that focus on specific pancreatic 

cancer issues to discuss with caregivers. 

• Conduct follow-up studies to assess 

patient satisfaction with information 

sources, tools, and decisions made, and 

on the impact of communication toolkits 

on patient choices, patient care, and 

patient satisfaction. 

3. Identify manpower requirements and 

costs of multidisciplinary clinical 

trials in pancreatic cancer. 

Currently, many health care providers forgo 

compensation for the time they spend 

participating in clinical research, which 

typically is non-reimbursable. This situation 

can erode the multidisciplinary teamwork 

28 Pancreatic Cancer: An Agenda for Action 
necessary to produce robust results from 

research on pancreatic cancer diagnosis, 

treatment, and patient outcome. It is 

important to facilitate the efficient and 

economic construction of a multidisciplinary 

infrastructure, not only for pancreatic cancer 

clinical trials, but for all types of cancer 

research. In addition, barriers to patient 

participation in clinical trials, such as 

expenses, travel, and time should be 

estimated and factored in to the 

infrastructure cost model for pancreatic 

cancer clinical trials. 

Recommendations 

• Identify personnel, time, cost, and 

material requirements for 

multidisciplinary trials in pancreatic 

cancer. 

• Conduct studies of patient and physician 

reimbursement in clinical trials in both 

fee-for-service and managed care 

settings. Studies of this nature will 

provide normative data for determining 

appropriate remuneration for 

participation from members of various 

health care plans. 

4. Determine the efficacy of current 

practices in pancreatic cancer 

diagnosis and care and evaluate new 

strategies for managing difficult 

treatment and end of life issues. 

Pancreatic cancer is an aggressive disease 

that swiftly robs patients of quality and 

quantity of life. The symptoms are 

particularly onerous and difficult to treat 

effectively. Additionally, because median 

life expectancy after diagnosis is six months 

or less, meaningful quality of life with this 

disease takes on extraordinary significance. 

Although the high mortality rate leaves few 

survivors, these survivors can provide 

valuable information about their experience 

that could help to provide hypotheses for 

research to improve many aspects of disease 

management for pancreatic cancer patients. 

The mortality rate of pancreatic cancer 

demands research on methods to assist 

patients, their families, and health care 

professionals in effectively managing the 

disease when one does survive and to assist 

with the transition to end of life care when 

this is necessary. Both the struggle for 

survival and the transition to end of life care 

are often marked by feelings of 

abandonment on the part of the patient and 

feelings of inadequacy on the part of 

families and health care providers. A 

strategic, coordinated research program is 

needed into methods of improving quality of 

life in the last months of life. Outcomes 

research that provides information on these 

issues is important to all phases of 

pancreatic (and most other) cancer research. 

Recommendations 

• Conduct empirical investigations 

targeting pancreatic cancer survivors: 

— Identify biological and behavioral 

variables common among pancreatic 

cancer survivors. 

— Determine whether there are markers 

or genetic changes associated with 

survival and/or recurrence. 

— Identify problems that may arise in 

long-term survivors. 

— Coordinate these studies with rapid 

autopsy programs, providing a tissue 

source and an opportunity for 

patients to contribute to the research 

effort. 

• Identify variables influencing quality of 

life, including: 

— Symptom management, including 

effects of complementary therapies. 

— Effects of support groups, 

educational interventions, or other 

support systems on quality of life. 

Research Priorities 29 
— Effects of patient quality of life on 

caregivers. 

— Special problems of the older patient. 

• Conduct quantitative and qualitative 

research studies that improve our 

understanding of end of life issues, 

including: 

— Hospice care/palliative care. 

— Caregiver knowledge and support. 

— Informed patient decision making. 

RESOURCES NEEDED 

1. Develop a survivorship registry to 

enable the study of relationships 

among survival, biological (e.g., genes, 

markers), and self-report data on 

patients beginning at diagnosis. 

2. Create a Web-based repository to 

track, update, and categorize 

information on pancreatic cancer 

clinical trial costs. This repository 

would be used by health services 

researchers and clinical researchers to 

determine normative costs associated 

with pancreatic cancer research. These 

data would be especially useful for 

estimating budget item costs, including 

manpower. 

3. Develop new models that can be 

applied and validated in community 

and academic research settings, 

including models for: 

• Analyzing cost and level of effort 

required to conduct clinical research in 

pancreatic cancer. 

• Assessing communication effectiveness. 

• Improving patient decision making. 

• Describing and summarizing consistent 

patterns of variables indicative of longer 

term survival of pancreatic cancer. 

• Characterizing quality of life (e.g., 

symptom management, family 

involvement) and end of life (e.g., 

hospice care, counseling) parameters for 

pancreatic cancer patients. 

4. Create new education, training, and 

communication tools, including: 

• Communication toolkits for health care 

providers with education components 

and collateral materials to enable 

professionals to better assist and support 

patient decision making. 

• Patient decision making toolkits that are 

culturally and linguistically appropriate 

and take into account various literacy 

levels and familiarity with 

communication technologies. 

• Mechanisms to facilitate increased 

interaction among health care providers, 

advocates, and professional and funding 

organizations. 

30 Pancreatic Cancer: An Agenda for Action 
III. Scientific Toolkit 
Scientific Toolkit

STATE OF THE SCIENCE 

The genetic alterations discovered thus far in 

human pancreatic adenocarcinoma provide a 

key starting point for understanding the 

biology of the disease, but we must complete 

our understanding of these lesions, of the 

predisposition-modifier genes, and the 

signaling pathways that play key roles in 

primary pancreatic tumor development. 

Moreover, although certain gene mutations 

have been linked to tumorigenesis, there 

exists no formal proof that these acquired 

mutations remain relevant to tumor 

maintenance. If they are relevant, their 

specific functions in tumor maintenance also 

are unclear. 

The pancreatic cancer research community 

has been hampered in its efforts to answer 

these and other crucial research questions by 

a dearth of essential tools and technologies 

needed to conduct the broad range of studies 

that will lead to progress against the disease. 

Specifically, a “scientific toolkit” is needed: 

• High quality human pancreatic tumor 

specimens and sampling techniques that 

permit analysis of minute quantities of 

biological samples. 

• Genetically tractable model systems to 

investigate the origins and progression of 

pancreatic neoplasia. 

• Minimally invasive imaging techniques 

to monitor disease progression and 

response to therapy. 

• Specific inhibitors of signaling pathways 

to define and dissect the role of 

individual pathways in the genesis and 

maintenance of pancreatic cancer and to 

validate targets for intervention. 

• Complete compendium of the genetic 

lesions important in pancreatic cancer. 

• Quantitative catalogs of the full spectra 

of gene expression patterns in normal 

and neoplastic pancreas. 

The following priority initiatives are 

proposed to address these deficiencies and 

support multiple avenues of the pancreatic 

cancer research effort: 

RESOURCE PRIORITIES 

1. Construct resources to provide access 

to a range of normal and neoplastic 

human pancreas samples. 

Organized and coordinated pancreatic 

adenocarcinoma registries, including family 

histories and extensive clinicopathological 

information, are urgently needed. These 

registries should be linked to coordinated 

resources for storing and distributing 

biological samples, including pre-invasive, 

invasive, and metastatic specimens that are 

equally well characterized. Such samples 

should include somatic non-cancerous 

tissues from affected individuals and their 

family members. In addition, the derivation 

of representative pancreatic cancer and 

mesenchymal cell lines is strongly 

encouraged to augment the current panel of 

cell lines available for xenograft 

tumorigenesis studies in nude mice and to 

allow modeling of stromal-epithelial cell 

interactions in vitro. To be of optimum use, 

these resources also should maintain one or 

more frequently updated databases of 

genome-wide studies, including expression 

profiling, DNA sequencing, in situ 

hybridization of tissue arrays, high density 

genotyping, and mutation analysis. 

Scientific Toolkit 31 
Establishing and coordinating these 

resources and databases will promote 

efficient and thorough utilization of these 

precious samples and enable investigators to 

obtain essential information without the 

need to build or develop advanced 

capabilities. Storage may be centralized or 

dispersed, depending on the exigencies of 

the specimens, as long as investigators have 

reasonable access to them. To enable rapid 

progress, a collaborative, multidisciplinary, 

multicenter approach is essential. Samples 

must be collected using a standard procedure 

with appropriate long-term storage 

techniques and quality control to maximize 

the usefulness of biological materials. 

Adequate compensation must be made for 

time, effort, and supplies to surgeons, 

research aides, pathologists, and others who 

provide appropriate oversight and procedural 

audits. 

2. Using this resource, construct a 

relational database containing 

information on the biological profiles 

of normal and abnormal pancreas 

cells. 

The resource described above should be 

used as the foundation for a “value-added” 

pancreas database containing data from 

allelotyping, DNA sequencing, cDNA 

expression analysis, tissue arrays, and 

proteomics studies. In addition, data should 

be gathered from studies exploring the 

strong intermingling of pancreatic cancer 

with stromal elements (desmoplastic 

reaction) and the stromal-epithelial 

interactions that likely play an important role 

in the pathogenesis and progression of this 

disease. The database also should include, 

when available, information on cancer cell 

karyotype, comparative genome 

hybridization, and signal pathway activation. 

These data will be collected for normal 

pancreatic ductal epithelial, acinar, and islet 

cells, primary and metastatic cancer cells, 

stromal cells, and where feasible, preinvasive lesions (PanIN). Such a database 

will provide an important tool for 

interdisciplinary and multi-institutional 

efforts to understand normal pancreas 

development, the genesis of preneoplastic 

lesions and their progression to invasive and 

metastatic carcinoma. 

A pancreatic cancer research Web page 

should be developed to make these data 

freely available to the scientific community, 

with links to a multitude of relevant 

bioinformatics tools to permit data access 

and analysis by all interested parties. This 

experimental database also should be 

constructed to allow rational queries to 

similar databases that are being constructed 

for other cancers. Issues of genomics 

analysis standardization (e.g., reference 

samples, antibody reagents) must be 

addressed. 

3. Develop biological sampling 

techniques that permit analyses of 

minute quantities of biological 

samples. 

The scarcity of biological samples of PanINs 

and invasive pancreatic cancers, and the 

infiltrating nature of their growth make it 

imperative to develop sampling techniques 

that will permit analyses of exceedingly 

small samples. 

4. Organize knowledge of signaling 

pathways into interrelated networks 

and systems to assess the ultimate 

outcome of alterations in the pathways 

found in pancreatic cancer. 

The perspective of individuals trained in 

systems analysis in other fields (e.g., 

mathematics, engineering, bioinformatics) 

should be applied to these biological 

networks. This process should start with 

pathways that currently are understood to 

32 Pancreatic Cancer: An Agenda for Action 
contribute to pancreatic cancer, expanding to 

interconnect pathways affected by genetic 

alterations and microenvironmental 

influences. 

5. Establish gene-based model systems in 

vivo and ex vivo that faithfully 

recapitulate the complex biology of 

human pancreatic adenocarcinoma. 

These models are needed to study signal 

transduction pathways and gene expression, 

to test early detection and diagnostic 

methods, and to develop novel diagnostic 

and therapeutic strategies. In addition, 

models are needed that will enable 

investigators to evaluate the role of key 

genetic alterations in the development of 

precursor lesions, tumorigenesis, 

maintenance, invasion, and metastasis. Such 

studies should include the construction of 

mouse model systems of pancreatic cancer 

in conjunction with the pre-existing NCI 

Mouse Models of Human Cancer 

Consortium and the study of normal and 

neoplastic human pancreatic ductal 

epithelial cells. Culture systems for 

identifying and propagating normal human 

pancreas stem cells, as well as ductal 

epithelial, acinar, and islet cells, are needed 

to study and define the biological phenotype 

of normal pancreas cells, define the changes 

that occur as pancreas epithelial cells 

progress from a pre-invasive to a fully 

malignant state, and characterize the cells 

from which pancreatic adenocarcinoma 

arises. (Other developmental systems, such 

as zebrafish and xenopus, were discussed 

but no consensus was reached on their use). 

It will be essential to apply the compendium 

of gene expression patterns and genomewide genotypes of pancreatic 

adenocarcinoma described above to the 

study of these new mouse models and, in 

turn, to use the models to expand the base of 

knowledge concerning relevant genotypes 

and gene expression patterns in pancreatic 

cancer. Although the Cancer Genome 

Anatomy Project (CGAP) is making 

significant progress with regard to human 

tumors, the genomics infrastructure to 

analyze the mouse lags far behind and a 

pancreatic ductal epithelial cell-specific 

promoter(s) has not been identified. These 

problems hamper efforts to rapidly isolate 

genes based on interspecies sequence 

homologies and generate mouse models for 

pancreatic cancer that require pancreas 

ductal epithelial cell-specific promoters for 

various tissue-specific strategies. Identifying 

such promoters quickly through functional 

genomics efforts in mice and humans is 

critical to facilitate model systems 

development. 

6. Develop imaging systems for 

elucidating pancreatic cancer biology 

and for detecting and monitoring this 

disease. 

Consistent with NCI’s Extraordinary 

Opportunity for Investment in Cancer 

Imaging, new imaging technologies should 

be developed (or existing technologies 

refined) to more fully analyze the form and 

function of the pancreas. Ideally, such 

functional and molecular imaging systems 

should distinguish benign from malignant 

pancreatic disease, and identify early preinvasive lesions and very small primary 

tumors as well as the extent of invasion and 

metastasis. In addition, these minimally 

invasive techniques may be helpful in 

determining pancreatic tumor response to 

conventional and novel therapies. They also 

should be designed for use in animal model 

studies aimed at developing and evaluating 

novel diagnostic and therapeutic agents. 

Scientific Toolkit 33 

Appendices
Appendix A: Pancreatic Cancer Progress Review Group 

Member Roster 

Scott Kern, M.D.

Johns Hopkins University

Co-Chair

Margaret Tempero, M.D.

University of California, San Francisco 

Co-Chair

Barbara Conley, M.D.

National Cancer Institute

Executive Director

James Abbruzzese, M.D.

University of Texas 

M.D. Anderson Cancer Center

Nazmi Volkan Adsay, M.D.

Wayne State University

Karmanos Cancer Institute

Teresa Brentnall, M.D.

University of Washington

Chusilp Charnsangavej, M.D.

University of Texas 

M.D. Anderson Cancer Center

Paul J. Chiao, Ph.D.

University of Texas 

M.D. Anderson Cancer Center

Douglas B. Evans, M.D.

University of Texas

M.D. Anderson Cancer Center

Jorge Gomez, M.D., Ph.D.

National Cancer Institute

Louise Grochow, M.D.

National Cancer Institute

Ernest Hawk, M.D.

National Cancer Institute

Tony Hollingsworth, Ph.D.

University of Nebraska Medical Center

Elizabeth A. Holly, Ph.D., M.P.H

University of California, San Francisco

Ralph H. Hruban, M.D.

Johns Hopkins Hospital 

Elizabeth Jaffee, M.D.

Johns Hopkins University

Murray Korc, M.D.

University of California, Irvine

Charles J. Lightdale, M.D.

Columbia University

College of Physicians and Surgeons

Albert Lowenfels, M.D.

New York Medical College

Martin McMahon, Ph.D.

University of California, San Francisco

Michael L. Meyers, M.D., Ph.D.

Aventis Pharmaceuticals

Cherie Nichols, M.B.A.

National Cancer Institute

Dan O’Hair, Ph.D.

University of Oklahoma

Gloria Petersen, Ph.D.

Mayo Clinic

Paula Kim Simper

Pancreatic Cancer Action Network, Inc.

Selwyn Maurice Vickers, M.D.

University of Alabama, Birmingham

Appendix A: Pancreatic Cancer Progress Review Group Member Roster 35 
Robert F. Vizza, Ph.D. 

Lustgarten Foundation for Pancreatic Cancer 

Research 

David Whitcomb, M.D., Ph.D. 

University of Pittsburgh Medical Center 

36 Pancreatic Cancer: An Agenda for Action 
Pancreatic Cancer Progress Review Group Roundtable 

Participant Roster 

Scott Kern, M.D.

Johns Hopkins University

Co-Chair

Margaret Tempero, M.D.

University of California, San Francisco 

Co-Chair

Barbara Conley, M.D.

National Cancer Institute

Executive Director

Roger Aamodt, Ph.D.

National Cancer Institute

James Abbruzzese, M.D.

University of Texas 

M.D. Anderson Cancer Center

Ross Abrams, M.D.

Johns Hopkins University

Nazmi Volkan Adsay, M.D.

Wayne State University

Karmanos Cancer Institute

Demetrius Albanes, M.D.

National Cancer Institute

Atul Bedi, M.D.

Johns Hopkins University

Lisa Begg, M.D.

National Cancer Institute

Al B. Benson, III, M.D.

Northwestern University

Patter Birsic

The National Pancreas Foundation

Diane Birt, Ph.D.

Iowa State University

Randall Brand, M.D.

University of Nebraska Medical Center

Teresa Brentnall, M.D.

University of Washington

William R. Brugge, M.D.

Massachusetts General Hospital

Lisa Rolfe Burik

Tiber Group

Kevin M. Callahan, Ph.D.

National Cancer Institute

Marcia Irene Canto, M.D.

Johns Hopkins University

Enes Carnesecca

Lustgarten Foundation

Donald Cegala, Ph.D.

The Ohio State University

Chusilp Charnsangavej, M.D.

University of Texas

M.D. Anderson Cancer Center

Paul J. Chiao, Ph.D.

University of Texas

M.D. Anderson Cancer Center

Karen Cleary, M.D.

University of Texas

M.D. Anderson Cancer Center

John Cole, III, Ph.D.

National Cancer Institute

JoAnn Coleman

Johns Hopkins Hospital

Appendix A: Pancreatic Cancer Progress Review Group Participant Roster 37 
Carolyn Compton, M.D., Ph.D.

McGill University

Adrienne Cox, Ph.D.

University of North Carolina at Chapel Hill

Ronald DePinho, M.D.

Dana-Farber Cancer Institute

Harvard Medical School

James DiSario, M.D.

University of Utah School of Medicine

Jeffrey Drebin, M.D., Ph.D.

Washington University School of Medicine

Lee Ellis, M.D.

University of Texas

M.D. Anderson Cancer Center

Bob Etemad, M.D.

University of Pittsburgh Medical Center

Douglas B. Evans, M.D.

University of Texas

M.D. Anderson Cancer Center

Jay Everhart, M.D. 

National Institute of Diabetes and Digestive 

and Kidney Diseases 

Olivera Finn, Ph.D.

University of Pittsburgh School of Medicine

Marsha Frazier, Ph.D.

University of Texas

M.D. Anderson Cancer Center

Gary Friedman, M.D.

Stanford University School of Medicine

Steven Gallinger, M.D.

Mount Sinai Hospital

Susan M. Gapstur

Northwestern University Medical School

Parviz Ghadirian, Ph.D.

University of Montreal

Sherwood Githens, Ph.D.

National Cancer Institute

Michael Goggins, M.D.

Johns Hopkins Medical Institutions

Leslie I. Gold, Ph.D.

New York University School of Medicine

Alisa Goldstein, Ph.D.

National Cancer Institute

Jorge Gomez, M.D., Ph.D.

National Cancer Institute

Constance Griffin, M.D.

Johns Hopkins University

Louise Grochow, M.D.

National Cancer Institute

Terri Hallquist, M.S.

National Cancer Institute

Ernest Hawk, M.D.

National Cancer Institute

Donald Henson, M.D.

National Cancer Institute

Tony Hollingsworth, Ph.D.

University of Nebraska Medical Center

Elizabeth A. Holly, Ph.D., M.P.H

University of California, San Francisco

Daniel Hoth, M.D.

Axys Pharmaceuticals, Inc.

Ralph H. Hruban, M.D.

Johns Hopkins Hospital

Elizabeth Jaffee, M.D.

Johns Hopkins University

38 Pancreatic Cancer: An Agenda for Action 
Richard Kaplan, M.D.

National Cancer Institute

Mary Keogan, M.D.

Harvard Medical School

Beth Israel Deaconess Medical Center

Young Kim, M.D.

University of California, San Francisco

David Klimstra, M.D.

Memorial Sloan-Kettering Cancer Center

Murray Korc, M.D.

University of California, Irvine

Steven Leach, M.D.

Johns Hopkins University

William Lee, M.D., Ph.D.

University of Pennsylvania

Charles J. Lightdale, M.D.

Columbia University

College of Physicians and Surgeons

Albert Lowenfels, M.D.

New York Medical College

Tracy Lugo, Ph.D.

National Cancer Institute

Herbert Lyerly, M.D.

Duke University Medical Center

Peter Marks, M.D., Ph.D.

Harvard Medical School

Lynn M. Matrisian, Ph.D.

Vanderbilt University School of Medicine

Cornelius McGinn, M.D.

University of Michigan

Martin McMahon, Ph.D.

University of California, San Francisco

Alec Megibow, M.D.

New York University School of Medicine

Neal Meropol, M.D.

Fox Chase Cancer Center

Michael L. Meyers, M.D., Ph.D.

Aventis Pharmaceuticals

Donald Mitchell, M.D.

Thomas Jefferson University Hospital

Kate Nagy, M.A.

National Cancer Institute

John P. Neoptolemos, M.D.

University of Liverpool

Alfred I. Neugut, M.D., Ph.D.

Columbia University

Cherie Nichols, M.B.A.

National Cancer Institute

Jeffrey A. Norton, M.D.

University of California, San Francisco

Dan O’Hair, Ph.D.

University of Oklahoma

Eileen O’Reilly, M.D.

Memorial Sloan-Kettering Cancer Center

G. Johan Offerhaus, M.D., Ph.D.

University of Amsterdam

Michel Ouellette, Ph.D.

The Eppley Institute

The University of Nebraska Medical Ctr.

Gloria Petersen, Ph.D.

Mayo Clinic

Kay Pogue-Geile, Ph.D.

University of Pittsburgh

Appendix A: Pancreatic Cancer Progress Review Group Participant Roster 39 
Vito Quaranta, M.D.

The Scripps Research Institute

Robert Radinsky, Ph.D.

Amgen, Inc.

Howard A. Reber, M.D.

University of California, Los Angeles 

Shrikanth Reddy, Ph.D.

University of Texas

M.D. Anderson Cancer Center

Mace Rothenberg, M.D.

Vanderbilt-Ingram Cancer Center

Bruce Ruggeri, Ph.D.

Cephalon, Inc.

Eric Sandgren

University of Wisconsin-Madison

Fazlul Sarkar, Ph.D.

Wayne State University

Karmanos Cancer Institute

Richard Semelka, M.D.

University of North Carolina

Debra Silverman, Ph.D.

National Cancer Institute

Paula Kim Simper

Pancreatic Cancer Action Network, Inc.

Joel Tepper, M.D.

University of North Carolina

Paula Termuhlen, M.D.

University of Nebraska Medical Center

Michael Tisdale, Ph.D.

Aston University

Charles Ulrich, M.D.

University of Cincinnati

Raul Urrutia, M.D.

Mayo Clinic

Annabelle Uy, M.S.

National Cancer Institute

George Vande Woude, Ph.D.

Van Andel Research Institute

Selwyn Maurice Vickers, M.D.

University of Alabama, Birmingham

Robert F. Vizza, Ph.D.

Lustgarten Foundation for Pancreatic Cancer

Research 

Joel Weissfeld, M.D.

University of Pittsburgh Cancer Institute

David Whitcomb, M.D., Ph.D.

University of Pittsburgh Medical Center

Jeffrey White, M.D.

National Cancer Institute

Christopher Willett, M.D.

Massachusetts General Hospital

Harvard Medical School

Rosemary Yancik, Ph.D.

National Institute on Aging, NIH

Melissa Yazman

Ian S. Zagon, Ph.D.

The Pennsylvania State University

40 Pancreatic Cancer: An Agenda for Action 
Appendix B: NCI-Supported Pancreatic Cancer Research 

Estimated NCI Support of Pancreatic Cancer Research, 1999

Scientific Area Estimated Level of Support* 

Cancer-Related Biology $ 5,115,000 

Etiology $ 2,173,000 

Prevention $ 1,310,000 

Early Detection, Diagnosis, and Prognosis $ 1,938,000 

Treatment $ 6,172,000 

Cancer Control, Survivorship, and Outcomes Research $ 134,000 

Scientific Model Systems $ 467,000 

Total $ 17,309,000 

* Source: NCI 

Appendix B: NCI-Supported Pancreatic Cancer Research 41

Appendix C: About the National Cancer Institute’s 

Progress Review Groups 

The National Cancer Institute (NCI) 

supports basic, clinical, and populationbased research to elucidate the biology, 

etiology, early detection, prevention, and 

treatment of cancers of various organ sites. 

These research efforts have produced a 

substantial base of knowledge that, while 

providing a wealth of new scientific 

opportunities that can further advance our 

knowledge and progress against these 

diseases, also requires that limited resources 

be used to their optimal advantage. 

To help ensure the wise use of resources 

with maximum benefit, NCI has established 

Progress Review Groups (PRGs) to assist in 

assessing the state of knowledge, reviewing 

the Institute’s research portfolio, and 

identifying scientific opportunities and needs 

within its large, site-specific research 

programs. 

CHARGE TO THE PRGS 

Each PRG is charged to: 

1. Identify and prioritize scientific research 

opportunities and needs to advance 

medical progress against the cancer(s) 

under review. 

2. Define the scientific resources needed to 

address these opportunities and needs. 

3. Compare and contrast these priorities 

with the current NCI research portfolio. 

4. Prepare a written report that describes 

findings and recommendations. 

5. Discuss a plan of action with NCI 

leaders to ensure that the priority areas 

are well addressed. 

The following section details the process 

used to execute these charges 

THE PRG PROCESS 

PRG members are selected from among 

prominent members of the scientific, 

medical, and advocacy communities and 

from industry to represent the full spectrum 

of scientific expertise required to make 

comprehensive recommendations for the 

NCI’s cancer research agenda. The 

membership is also selected for its ability to 

take a broad view in identifying and 

prioritizing scientific needs and 

opportunities that are critical to advancing 

the field of cancer research. 

The leadership of each PRG finalizes an 

agenda and process for a PRG Planning 

Meeting. At the Planning Meeting, 

participants are identified to take part in a 

subsequent Roundtable meeting. Topics are 

identified for Roundtable breakout sessions 

to which participants will be assigned and 

for which the PRG members will serve as 

co-chairs. 

A PRG Roundtable brings together in an 

open forum approximately 100 to 180 

leading members of the relevant cancer 

research, medical, industry, and advocacy 

communities to formulate key scientific 

questions and priorities for the next five to 

ten years of research on specific cancers. As 

part of the process, the NCI provides the 

PRG Roundtable an analysis of its portfolio 

of cancer research in the relevant organ site. 

This analysis is intended to enable the 

Roundtable to compare and contrast 

identified scientific priorities with the 

research currently being done under the 

Institute’s auspices. Input from the 

Appendix C: About the National Cancer Institute’s Progress Review Groups 43 
Roundtable is used by the PRG in 

delineating and prioritizing 

recommendations for research, related 

scientific questions, and resource and 

infrastructure needs. At its discretion, the 

PRG may solicit additional input from the 

research and advocacy communities through 

workshops, ad hoc groups, or by other 

means. The PRG also may consider the 

deliberations of previously convened expert 

groups that have provided relevant cancer 

research information. 

THE PRG REPORT 

After the Roundtable, the PRG’s 

recommendations are documented in a draft 

report, multiple iterations of which are 

reviewed by the PRG leadership and PRG 

members. The final draft report is then 

submitted for deliberation and acceptance by 

the NCI Advisory Committee to the 

Director. Finally, the PRG meets with the 

NCI Director to discuss the Institute’s 

response to the report, which is then widely 

disseminated and integrated into the 

Institute’s planning activities. 

PRG reports on breast cancer, prostate 

cancer, colorectal cancer, and brain tumors, 

and this report on pancreatic cancer, are 

available online at osp.nci.nih.gov/Prg_assess. 

Other PRG reports currently in development 

or being planned include reports on 

leukemia, lymphoma, and myeloma; 

gynecologic cancers; and kidney and bladder 

cancer. 

44 Pancreatic Cancer: An Agenda for Action 
NIH Publication Number 01–4940
 February 2001 T476