Overview of the AACR Clinical and Translational Cancer Research Think Tank Meeting
Authors: Kenneth C. Anderson, Raymond N. DuBois
Journal: Clinical Cancer Research (2012)

On January 17–18, 2010, the American Association for Cancer Research (AACR) hosted a Think Tank meeting in San Francisco that brought together a group of clinical and translational research thought leaders to identify the most promising scientific priorities and opportunities for the future of this field. This meeting was held over 2 days and included specific presentations on key areas such as animal models; the impact of genomics on personalized cancer therapy; innovative clinical trial design; imaging strategies, controversies, and opportunities; and biomarkers and companion diagnostics. Breakout sessions focused on research, information sharing, standardization, validation, regulatory issues, and education. The overall goal of this gathering was to provide a forum for thoughtful input and discussion about the strategies needed to help catalyze progress in the field of clinical and translational cancer research.A number of key issues were discussed over this 2-day period, and several opportunities and barriers were identified. The group reached a general consensus regarding the following needs: (i) establishment of a national database to provide access to clinical trials data, biomarker data, and educational information for researchers, providers, decision makers, and the public; (ii) additional support for team science in the academic, private, and governmental sectors; (iii) mechanisms for sharing data and approaches more effectively; (iv) education of the research, advocacy, and decision-maker communities about the current and future challenges of clinical and translational cancer research; (v) involvement and engagement of survivors and advocates in supporting team science and clinical/translational research in general; (vi) biomarker-driven clinical practice for both cancer prevention and treatment; and (vii) outreach and involvement of the pathology community, especially in the area of biomarker development to help establish better standards and adopt new science.An ongoing challenge in the field is to develop the most effective strategies for using biomarkers and companion diagnostics to effectively direct the care of cancer patients who are undergoing treatment with targeted therapies. The group also viewed the lack of appropriate funding as the primary challenge in translational research, followed by clinical trial design and the cost-effectiveness of cancer prevention.Dr. Susan Desmond-Hellmann gave the keynote address at a meeting entitled “Accelerating Innovation: Oncology Translational Research.” She reviewed the progress in the field and remarked on certain guiding principles that will be critical for the future. She stated that rituximab, trastuzumab, and imatinib mesylate are 3 drugs that have changed cancer medicine because they each address a major unmet need, are based on biomarker-driven patient selection, can extend survival, and are well tolerated by patients. She noted that the barriers that currently make cancer research so slow, expensive, inefficient, and uncertain must be addressed if additional similar products are to be developed. Going forward, she noted that the most important metric for success should be predictability; specifically, cancer researchers have not gone far enough to decrease uncertainty, and this is a technical challenge that needs to be overcome.Currently, the ultimate failure rate for the development of new cancer drugs is exceedingly high. Enormous resources are expended to get a drug candidate from the point of basic discovery to the preclinical testing stage and finally to the patient. Primarily, the current paradigm for drug development does not effectively rule out poor drug candidates early on in their development. Over the next decade, cancer researchers must strive to better understand the biologic drivers of cancer and explore novel approaches to bench-to-bedside research. To build the next generation of nimble, flexible investigators, today's leaders must value, espouse, and teach new methods and models for research that stress the importance of translational research.The Think Tank meeting included some very productive breakout sessions in which recommendations were made to improve the effectiveness of clinical/translational research overall. Each group was charged with defining top priorities, summarizing the state of the science, identifying obstacles and challenges, and recommending new directions and opportunities for progress.Five breakout groups discussed the following areas:The following is a synthesis of the breakout groups' reports, in which common themes are identified and recommendations are summarized according to the potential action area.The cancer biology and drug-development breakout group focused on many challenges facing investigators. The group expressed concerns regarding the lack of predictable animal models, a lack of understanding of the magnitude of tumor heterogeneity, and whether a specific subset of cells, such as tumor-initiating cells, should be the appropriate target for therapy. The group noted the need to better integrate basic and clinical scientists, and to strengthen academic–industry partnerships. One overriding theme was the need for data to be available to and interpretable by scientists. This will require the availability of national databases that include tools for analysis, well-defined data elements, and strict quality standards. If the scientific community identifies this as a significant need, nonprofit organizations (such as SU2C) could be approached for support. A similar effort could be made in the area of patient access to clinical trials and clinical information. The AACR could fill several roles, including policy, advocacy, and education. For example, the AACR could coordinate a national and international network for data infrastructure or develop a clinical trials website that would provide information to patients in a different and more comprehensive way than is currently available.The biomarker and clinical trials breakout group identified major areas for improvement as the foundation for progress. Currently, biosamples are acquired, stored, and annotated in a nonstandardized and not necessarily optimized fashion. Standards, guidelines, and blueprints are needed, especially for biospecimen collection. Although this has been clear for some time, the effort to achieve standardization faces significant hurdles stemming from the lack of data to support an evidence-based standard operating procedure, the lack of an arbiter to enforce standardization, and the existence of numerous local standards that have been in place for some time. To really enforce new standards, we must change professional behavior by establishing some combination of requisite procedures and training for accreditation, paying providers to follow protocols (through the Centers for Medicare and Medicaid Services), and educating providers about the use and importance of quality sample collection. New methods of collecting biosamples, such as circulating tumor cells and plasma DNA, should be developed and standardized. In addition, we need to develop systems to provide ready access to and release of biosamples needed to validate biomarker testing. Regulatory pathways to incentivize personalized biomarkers are now being established and should be refined to optimize integration into clinical trials. As drugs and therapies become more targeted, we will need to develop new statistical methods to identify effects and adverse events in small populations. In addition, adaptive trial designs that include a discovery phase and a validation phase will reduce the study time and allow researchers to focus on the most promising outcomes.The breakout group for targeted therapies focused on the need to identify susceptible populations to maximize the efficacy of targeted therapy. There is a need to identify, at a minimum, populations of patients who will not respond to treatment, and thereby enrich clinical trials with patients whose disease is more likely to be susceptible to the new therapy. This will also reduce the costs of clinical trials and health care and avoid unnecessary side effects. The group foresaw a need for better databases to input test data and link them to outcome data.Two additional areas were highlighted that need further incentives for study in the development of targeted therapies. Combination therapies are difficult to develop, particularly if only marginal results are obtained in the initial stages of single-agent trials. Companies often lose interest before the biology of the new agent has been fully explored. A second area is the need to evaluate how a particular molecular target evolves over time, that is, whether new mutations or adaptations occur that can alter the response to targeted therapy. This requires a detailed analysis of the pathways that surround or bypass individual protein targets.The imaging breakout group discussed the importance of linking imaging targets to susceptibility genes, therapeutic targets, and outcome measures. They noted the need to identify new imaging targets, such as those located in the tumor microenvironment. A new approach would be to include the radiation-oncologist community in imaging activities. New probes to image specific components of tumor metabolism are being developed, and imaging is becoming increasingly important for direct radiation therapy and monitoring of tumor response.The group noted some important obstacles to the application of imaging agents in clinical trials and the clinic, including cost, the complexity of validation, and the regulatory pathway to FDA approval. A number of currently available imaging techniques are not being used in clinical trials because of cost and patient burden. In fact, the group noted that the per-patient cost of positron emission tomography could be twice as much as the entire per-patient cost of a clinical trial. The group expressed the hope that the AACR could take the lead in advocating a mitigation of imaging costs for clinical trials. In addition, the AACR could get involved early in the development of imaging technologies to convene stakeholders in order to focus efforts on tools that address the relevant health care questions and are scalable, patient focused, and reasonably priced.The prevention breakout group discussed the need for early recognition and treatment of disease. Thanks to early diagnoses, it is becoming possible to identify patients who do not require dramatic treatment. However, true prevention through risk assessment is still in its infancy. It is unclear where intervention is appropriate. Predictive markers are embryonic. To date, there has been limited engagement on the part of industry. Opportunities for progress lie in the integration of prevention, secondary prevention, early detection, and treatment. The group raised the idea of a patient-oriented website that would allow individuals to enlist in a registry and perhaps submit simple biologic samples. The resulting database could be used for tracking, education, and information dissemination.The group suggested that the AACR should establish multidisciplinary teams to integrate approaches to prevention. The organization could take a leadership role in using cancer vaccines to eradicate cancers that are caused by viruses. In examining cancer, the AACR must see it as a global health problem, and could support immunologic approaches to decrease the cancer burden worldwide.It is clear from the discussions highlighted above that much work remains to be done. Several general themes emerged, including the need for a national database to provide access to clinical trial data and biomarker data; the need to support team science more broadly; the need to share data, methods, and standards for biomarker development; and the need to engage advocates and survivors in supporting clinical/translational research. The following is an overall assessment of the highest-priority issues raised and discussed during the Think Tank meeting.The presentations and breakout sessions of the Think Tank meeting focused on current barriers to cancer research and led to a thoughtful discussion about the best approaches to take moving forward. Because some time has passed since the original meeting was held, we have elected to provide timely updates on these key areas from individuals who participated in that meeting, as well as other experts in the field. We have compiled five thoughtful mini-reviews on key issues under the following titles: (i) “Impact of Genomics on Personalized Cancer Medicine,” by Arteaga and Baselga; (ii) “Making Personalized Cancer Medicine a Reality: Challenges and Opportunities in the Development of Biomarkers and Companion Diagnostics,” by Parkinson, Johnson, and Sledge; (iii) “Genetically Modified Mouse Models for Biomarker Discovery and Preclinical Drug Testing,” by Kucherlapati; (iv) “Imaging: Strategies, Controversies, and Opportunities,” by Blasberg and Piwnica-Worms; and (v) “Reports from the 2010 Clinical and Translational Cancer Research Think Tank Meeting: Design Strategies for Personalized Therapy Trials,” by Berry, Herbst, and Rubin.We have only been able to touch on a few important areas we believe are critical for the future development of clinical and translational cancer research. We hope that you enjoy this CCR Focus section, and, more importantly, that it stimulates much-needed progress in the field.