# Presentation: 184421

## NCI Director’s Update

- NCI Director’s Update

- Dr. John E. Niederhuber
- Director, National Cancer Institute

- Board of Scientific Advisors
- March 3, 2008

## Why What We Are Doing is So Important

- 1,444,920 Americans were diagnosed in 2007
- 559,650 died of cancer in 2007
- $206.3 billion spent         on healthcare costs         for cancer in 2006
- 47 million Americans lack health insurance

- Human and Economic Burden of Cancer

- 2007 1,444,920

- 1998 1,228,600

- Estimated # of New U.S. Cancer Cases

## Cancer Death Rates

**1990**

**1995**

**2000**

**2005**

**225**
**220**
**215**
**210**
**205**
**200**
**195**
**190**
**185**
**180**
**175**

**Rate per 100,000 (NCI)**

**Number of cancer deaths (ACS)**

## Estimated Number of Cancer Survivors in the United States

- 11,941,043 survivors in 2007

## ?

- NCI’s Congressional Appropriations

**$2.5**

**$2.9**

**$3.3**

**$3.8**

**$4.2**

**$4.6**

**$4.8**

**$4.9**

**$4.8**

**$4.8**

**PB $4.8**

**?**

**$4.8**

**Dollars in billions**

## NCI’s Challenge

**$4.8B**

**$3.9B**

*** BRDPI: Biomedical Research and Development Price Index**** (****http://officeofbudget.od.nih.gov****)**

**Funds available**

**Adjusted by BRDPI***

**-19% loss in purchasing power since 2004**

**Dollars in billions**

- NCI budget in FY1998 = $2.3B

## Director’s Update

- NCI FY08 budget
- President’s budget FY09
- Some thoughts about the future

## NCI FY 2008 Operating Budget Development

**(dollars in thousands)**

| FY 2007 operating budget | $4,797,639 |
| --- | --- |
| FY 2008 appropriation | $4,805,088 |
| Difference ’07 to ’08 |         $7,449 |
| Percent Change ’07 to’08 |        +0.16% |

## NCI FY 2008 Operating Budget Development

**Less Est. NIH Taps/Assessments**

- Potential NIH Director’s 1% Transfer

**?**

- Potential DHHS Secretary’s Transfer

**?**

**-20,000**

- -0.26%

**Subtotal Available**

- -12,551

**Percent**
**change**

- 0.16%

**Subtotal Available**

- $7,449

**     ****Amount**
**(in thousands)**

**Notes:**
We have a placeholder for potential transfers by the NIH Directory or by the HHS Secretary.  We haven’t heard of any but they could happen.

Increase in Roadmap contribution to $43 million

Increase in taps and assessments.  Hopefully, $33 million is high but we won’t know all of them until this summer.  Last year increase was about $20 million 

## NCI FY 2008 Operating Budget Development

**Subtotal Available**

- 1.44%

**NCI-wide Requirements:**

- Mandated Salary Increases

**- 21,500**

- Rent/Lease/Utilities/Renovations Incr

- - $12,551

**- 10,000**

**Subtotal Available**

- - 69,051

-  -0.26%

**Percent**
** ****change**

**    ****Amount**
**(in thousands)**

- Small Business Program Increase

**0**

**NCI Director’s Reserve**

**- 25,000**

**Notes:**
We’ll set aside funds to pay the mandated salary increases and increases in rent

We have also added funds to RPGs to meet the NIH funding policies

Director’s Reserve

So what are the next steps?

## NCI FY 2008 Operating Budget Development

- SPORES

- Centers

**Subtotal Available**

- - 1.44%

- - $69,051

- - 7,855

- -3,588

- - 1.98%

**Subtotal  Available**

- -94,998

**Partial Restoration of Cuts**

**Percent**
** ****change**

**    ****Amount**
**(in thousands)**

- Coop Groups/CCOPs

- -8,504

- Infrastructure Restorations/Increases

- -6,000

## NCI FY 2008 Operating Budget Development Process

- NCI leaders evaluated programs with an eye toward reduced or flat budgets ahead
- FY08 operating budget target for each Division, Office and Center (DOC) is based on a 3% reduction
- Created a pool of funds for NCI-wide mandatory increases and reallocation for specific initiatives

## NCI FY 2008 Operating Budget Development

- Phaseouts/Reductions Res DOCs

**Subtotal Available**

- - 1.98%

- - $94,998

- 49,382

- $55,526

- Available for New Initiatives/
- Expansions/Restorations

**Potential Recoveries/Redeployments: **

- Noncompeting RPGs

- 46,228

**Percent**
** ****change**

**     ****Amount**
**(in thousands)**

- Competing RPGs

- 8,136

- Phaseouts/Reductions Infrastructure

- 6,778

- NCI-Frederick Redeployment

- 40,000

## NCI FY 2008 Operating Budget:     NCI Operating Policies

- NCI operating policies
- 1% inflationary adjustments on non-competing grants
- ~2% decrease from commitment for non-modular grants
- No cut to modular non-competing grants
- NCI to award fewer competing RPGs than FY 2007 (1,312 to 1,283)

**Notes:**
All NCI operating policies are aligned with the “Published NIH Guidelines”
NIH plans to award fewer competing RPGs than in FY07
-10,323 competing RPGs in 07
-projected 9.711 in ’08 – a reduction of 5.3%
NIH has reduced the number of grants to be awarded and allowed Institutes more flexibility on how to manage modular Type 5’s largely due to an outcry by the IC Directors.  Cutting new and non-competing grants in order to continue to increase the number of awards severely diminished the quality of research able to be conducted.

## NCI FY 2008 Operating Budget:     NCI RPG Policies

- NCI RPG policies
- Type-2 (competing continuing grants) will receive 3% above current levels
- Type-2 modular grants recommended for 7 modules or fewer will receive 5% above current levels
- Type-1 (new competing grants) will be   cut ~17%

**Notes:**
Notes:  Type 2’s will receive 3% above current levels which in most cases is last year’s award.  UNLESS the PI requested less than 3% or per review recommend less than 3%
Type-1’s will be cut 17% from the level requested and approved by peer review

## NCI FY 2008 Operating Budget:     NCI RPG Paylines

- NCI RPG Paylines
- R01: 12th percentile (14)
- *R01s: 19th percentile (will hit NIH target)
- Large R01s (over $700K):
- 14th percentile for 1st and 2nd rounds
- TBD for 3rd round
- P01: Selected on a case-by-case basis

**Notes:**
R21:  14th percentile
R03:  210 priority score
R33:  155 priority score

## Examples of Downsized and Stopped Programs

- Office of Centers, Training, and Resources
- Integrating Aging and Cancer Research (co-funded with NIA)
- NCI funding of $4M-$5M will not be renewed
- Supplements for Imaging Response Assessment Teams in Cancer Centers
- NCI funding of $2M will not be renewed

**Notes:**
Integrating Aging and Cancer Research project’s objective was to expand the knowledge base on aging- and age-related aspects of cancer in older persons.

Supplements for Imaging Response Assessment Teams in Cancer Centers’ main purpose is to advance the role of imaging in assessment of response to therapy.

## Examples of Downsized and Stopped Programs

- Div. of Cancer Control & Population Sciences
- Transdisciplinary Tobacco Use Research Centers
- FY2008 is final year of RFA, funded at $7.2M. No proposed RFA renewal
- NCI is joining a NIDA PA; For TTURC program, anticipate spending $2M-4M, rather than $7.2M/yr
- Long Term Cancer Survivors research RFA
- FY2008 funding reduced by $1.7M

**Notes:**
TTURCs are a multiIC collaborative led by NCI

## Examples of Downsized and Stopped Programs

- Division of Cancer Prevention
- CCOP cancer treatment trial accrual
- FY05: 7,948 patients
- FY06: 6,402 patients
- FY07: 6,100 patients (estimate)
- CCOP cancer prevention & control trials:
- FY05: 5,211 patients
- FY06: 4,994 patients
- FY07: 4,500 patients (estimate)

**Notes:**
In the last few years, the budgets have been held constant or decreased due to funding restrictions; CCOPs have had to reduce staff and, subsequently, their accrual.

## Examples of Downsized and Stopped Programs

- Division of Cancer Treatment and Diagnosis
- CTEP Interdisciplinary Research Teams for Molecular Target Assessment
- Eliminated in FY07; $1.4M
- Cancer Imaging Program’s Development of Contract Imaging Drugs and Enhancers
- Eliminated in FY07; $1.6M
- Cancer Diagnosis Program: breast and prostate cancer tissue resources unfunded or eliminated
- Prostate eliminated FY07; breast unfunded extension (combined max. funding $3.25M/yr)

## Examples of Downsized and Stopped Programs

- Division of Cancer Treatment and Diagnosis
- Data Resource for Analyzing Blood and Marrow Transplants
- Approved for funding at proposed level for FY08 ($600K)
- ~80% of proposed level for FY09 – FY12 (savings of approximately $470K each fiscal year)

## FY 2009 President’s Budget

**(dollars in thousands)**

| FY08 NCI appropriation | $4,805,088 |
| --- | --- |
| FY 2009 PB for NCI | $4,809,088 |
| Difference ’08 to ’09 |          $4,000 |
| Percent Change ’08 to’09 |            +0.1% |

**Notes:**
Total NIH President’s Budget (PB) request is $29.5 billion – flat with the FY 2008 Omnibus Appropriation

NCI PB is $4.8 billion - $4.7 million or .1% higher than the FY 2008 Omnibus

NIH Roadmap in FY 2009 is $534 million – an increase of $38 million or 7.7%.

## TRWG Implementation

- Dr. Lynn Matrisian (co-chair of the TRWG) now at NCI on an IPA
- Integrating with the CCCT
- Translational Research Operation Committee planned
- Established under the Clinical Trials Advisory Committee (a Federal Advisory Board)

**Notes:**
In notes:  This meeting will be immediately following the AACR Annual Prevention Meeting scheduled for November, 2008 in Washington.  AACR is also launching a new Prevention Journal in 2008.  All this coincides with Ray DuBois’s Presidential Year.

## Translational Research Working Group Goals

- Improve coordination and collaboration and instill a culture of active, goal-oriented management
- Improve identification of the most promising early translation research opportunities
- Tailor new and existing programs to facilitate early translational research progress
- Enhance operational efficiency and effectiveness

**Notes:**
In notes:  This meeting will be immediately following the AACR Annual Prevention Meeting scheduled for November, 2008 in Washington.  AACR is also launching a new Prevention Journal in 2008.  All this coincides with Ray DuBois’s Presidential Year.

## Cancer Centers Program
Remain in the Office of the Director
Organ Systems Branch (SPOREs)
Moving to the Division of Cancer Treatment and Diagnosis
Training Branch
Transition specific programs to the Divisions

- Cancer Centers Program
- Remain in the Office of the Director
- Organ Systems Branch (SPOREs)
- Moving to the Division of Cancer Treatment and Diagnosis
- Training Branch
- Transition specific programs to the Divisions

- Office of Centers, Training, and Resources

## Drs. Jim Doroshow and John Niederhuber will oversee the SPOREs
Continue monthly teleconference calls with SPORE Executive Committee
Dr. Toby Tucker Hecht named acting head during national/international search for new SPORE director
Dr. Jorge Gomez will lead a new NCI initiative to enhance global research and clinical trials participation in Central and South America

- Drs. Jim Doroshow and John Niederhuber will oversee the SPOREs
- Continue monthly teleconference calls with SPORE Executive Committee
- Dr. Toby Tucker Hecht named acting head during national/international search for new SPORE director
- Dr. Jorge Gomez will lead a new NCI initiative to enhance global research and clinical trials participation in Central and South America

- SPOREs Leadership

## Role of Clinical Research Center 

- Role of Clinical Research Center

- Continue to strengthen Medical Oncology
- Recruiting new chief of Laboratory of Pathology
- Pathology space renovations in Bldg 10
- Developing an Oncology Imaging Center
- Exploration of a Satellite Center at Suburban Hospital
- Strengthening fellowship training
- Participation in rare diseases clinic

- NCI Initiatives

**Notes:**
Develop a trans-NIH initiative on inflammation, immunology and autoimmunity  to bridge the separation between basic immunologists and physicians who care for patients with immune-mediated and autoimmune diseases. 

Facilitate interesting cases or patients with rare or difficult problems to be see at the CRC by creating screening protocols across Institutes.

Emphasize recruitment and retention of Clinical Investigators – create a culture and reward system based upon team science. 

6 subcommittees – each chaired by an IC Director
Also looking at infrastructure (core resources and identification of barriers to clinical research); looking at the CRC in the CTSA structure; facilitating extramural collaborations at the CRC> 

## Annual Translational Research Meeting

- Replace the summer SPORE meeting with an annual meeting
- Co-Chaired by Drs. Sheila Prindiville and Lynn Matrisian
- Planned for the Fall 2008 in Washington, D.C.

## The SBIR Bridge Award in Drug Development

**Commercialization**

**NDA**
**Review**

**Clinical**
**Trials**

**Safety**
**Review**

**Preclinical Development**
**(Lead Development, Animal Studies, File IND)**

**Target Identification**
**& Validation**

**Private Investment**

**Notes:**
Recommendations:
Bridge SBIR Projects Toward Commercialization (Phase IIB Bridge Awards)
Establish an SBIR Development Center (consolidating SBIR and STTR) – Open to other ICs
Focus Solicitation on Commercially Viable Technologies (Between FY07 and FY08 NCI increased the total number of contract proposals by 43%)
Assemble an Advisory Committee

SBIR = Small Business Innovation Research
STTR = Small Business Technology Transfer Program

## Theoretical Physics

- Feb. 26-28, 2008
- Workshop to explore opportunities to incentivize collaborations
- Leaders in physics, chemistry, mathematics and cancer research

## An Unprecedented

- Era of Discovery
- A transformation in medicine

## Tumors are “organs” composed of many interdependent cell types

**Tumors are “organs” composed of many interdependent cell types**

- Growth factors produced in adjacent cells promote cell proliferation and survival
- Cytokines and chemo tactic factors produced by inflammatory cells and other stroma promote cell migration and invasion
- Proteases produced by the mE break down basement membrane, altering the architecture of tissue structures and migration/invasion of tumor cells

- Growth and survival factors

- Cytokines and chemo tactic factors

- ECM

- Proteases

- Factors produced in cells within the tumor microenvironment can alter aspects of tumor cell behavior

- Ca stem cell

**Notes:**
Extracellular matrix
Immune system
Vascular system

## New Blood Vessel Growth Into Tumor

## Real-time PCR validation of microRNA profiling data

- Upregulated in cancer
- fibroblasts

- Downregulated in cancer
- fibroblasts

- Downregulated in cancer
- fibroblasts

## MicroRNA profiling results

| Name | P-Value | Average Consistent Fold Change |
| --- | --- | --- |
| hsa-miR-503 | 0.0072 | -1.88 |
| hsa-miR-424 | 0.0015 | -1.81 |
| hsa-miR-146a | 0.0015 | -1.80 |
| hsa-miR-181b | 0.0072 | -1.80 |
| hsa-miR-542-3p | 0.0072 | -1.57 |
| hsa-miR-638 | 0.0072 | -1.54 |
| hsa-miR-29b | 0.0266 | -1.50 |
| hsa-miR-127 | 0.0266 | 1.53 |
| hsa-miR-148a | 0.0266 | 1.57 |
| hsa-miR-224 | 0.0002 | 1.61 |
| hsa-miR-31 | 0.0072 | 3.66 |

- Higher in cancer
- fibroblasts

- Higher in normal
- fibroblasts

- Out of 553 human microRNA spotted on the chip, 11 showed more than a 1.5-fold difference between normal and cancer fibroblasts with the P-value < 0.027

**Niederhuber Lab**

## Diagnostics

- Therapeutic
- Developments
-  Gene Therapy
-  Drug Therapy

- Preventive
- Medicine

- Disease with Genetic Component

- Accelerated
- by Human
- Genome Project
- and HapMap

- Identify Genetic Defect(s)

- Pharmaco-
- genomics

- Time

## Functional Genomics

**Alterations in cellular function**
**Cell biology and                                  protein carbohydrate     chemistry**
**Regulation of                          gene expression**
**Whole genome                  sequencing**
**Genome-                                      wide                                association                             studies**

**Normal vs. abnormal phenotype**

**Genes and environment**

**Germline markers of risk**

**Somatic mutations**

**Therapy**
**Prevention**

**Behavioral science**

**Populations w/ disease (environmental risk exposure)**

**Large populations**
**Longitudinal history**

## A Physicist’s Insight into Biology 

- A Physicist’s Insight into Biology

**Erwin Schrödinger**

- “It is not that the subject (biology) was simple enough to be explained by mathematics, but rather that it was much too involved to be fully accessible to mathematics.”
- 				1944

## “Biology is more like history than it is like physics. You have to know the past to understand the present, there is no predictive theory of biology just as there is no predictive theory of history. The reason is the same; both subjects are too complicated for us.”
					Carl Sagan

- “Biology is more like history than it is like physics. You have to know the past to understand the present, there is no predictive theory of biology just as there is no predictive theory of history. The reason is the same; both subjects are too complicated for us.”
- 					Carl Sagan

## What can physics, physical chemistry, and applied mathematics bring to cancer biology? 

## Paul Davies, Ph.D.

- Director                  Beyond Institute    Arizona State University
- Keynote Presentation: “Confronting Complexity: Cancer at the Intersection of Physics and Biology”

## The technology of the complex future

- biotechnology

- nanotechnology

- quantum technology

- cancer

## Theoretical physics

- New conceptual insights into complex systems
- Experience with modeling computational complexity
- Ability to extract a signal from confusing noise
- Ability to “stand back” and see the system as a whole
- Tendency to ask really dumb questions, seemingly without embarrassment
- Salamander limb regeneration
- How do cells stick together, and why do metastasized cells come unstuck?
- Tolerance of “wild ideas”

## Robert Austin, Ph.D.

- Professor of Physics                  Princeton University
- Keynote Presentation: “21st Century Physics—Relevant Intersections With Barriers in Oncology”

## Donald Coffey, Ph.D.

- Professor of Urology; Oncology; Pathology and Pharmacology; and Molecular Sciences                   Johns Hopkins Univ.
- Keynote Presentation: “The Physical Sciences and Cancer Biology—Early Glimpses Across the Frontier”

## TWO TYPES OF INFORMATION FLOW WITHIN A CELL

**DIFFUSION**

- Soluble

**GRADIENTS**
**OSCILLATORY**
**B-Z Reactions**

- Structural

**VECTORAL**

**CHEMOMECHANICAL**
**VIBRATIONAL**
**TENSEGRITY**

## ?

- End view of DNA helix
- (10bp)

- Snowflake

- Human

- Thermodynamics
- Complexity
- Simplicity
- Symmetry
- Self Organization
- Information transfer
- Far from equilibrium
- Emergent property
- Non-linear
- Fractal
- Chaos
- Order
- Increased rate of entropy
- Evolution

- CANCER

## Ideas for Involving the Physical Sciences in Cancer Research

- We lack a field of Theoretical Cancer Biology
- Tumor cell complexity in association with the microenvironment requires mathematical models (cell communication, metastasis)
- Impact of basic physical principles and laws on cancer (mechanical forces, energy and energy transfer, cell shape, dimensions of time)
- The role of tumor cell evolution

## www.cancer.gov

**www.cancer.gov**

## Slide 50