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Physical Sciences-Based Frontiers in Oncology: A New Look at Evolution and Evolutionary Theory in Cancer

Overview | Meeting Objectives | Agenda | Readings

Overview

meeting report

Cancer is a devastating disease with an almost unfathomable impact individually on its victims and on populations worldwide. Cancer will take the life of 25 percent of the U.S. population; one in two men and one in three women will die from cancer. The potential impact of the aging of the baby boomers and other demographic effects will produce a significant increase in the numbers of new cancer cases (estimates range from 30 to 40 percent) in the next 10-20 years - at an ever increasing cost to our citizens. The NCI estimates that the economic impact of cancer in the United States is currently approximately $200 billion and we do not yet have a clear picture of how the increases in new cancer cases will translate into health care costs, but the potential is daunting. On the positive side, the cancer research communities, perhaps the largest group of scientists ever engaged in studying a specific disease, are generating data on many levels about cancer at an unprecedented pace.

Knowledge about cancer, hard won over the last few decades, is providing an ever increasing but fragmented picture of this complex of diseases at the genetic, molecular, and cellular levels. Translation of this knowledge into new cancer interventions has been, and remains, slow for a number of reasons, ranging from lack of U.S. infrastructure for translational research to the under-resourced development of science-based regulatory processes. Despite substantial progress in the biomolecular science of cancer, mortality rates have not improved much over the last several decades.

Cancer is classically defined as a disease of genetic alterations (inherited and acquired) and described as cells growing out of normal regulatory control. There are hundreds, perhaps thousands, of genetic changes in the over 200 diseases comprising cancer. Some of these mutations are critical to the cancer process (driver mutations) while others apparently are not (passenger mutations). These changes in the genome are translated into new messenger molecules and proteins that populate the intricate networks and signaling pathways that drive the function of both normal and cancerous cells, tissues, organs, and organisms. Describing and ultimately predictably understanding these integrated, often redundant, networks in normal and cancer cells represent two of the greatest interrelated scientific challenges of our time. It should also be noted that although cancer cells proliferate outside the realm of normal cellular regulation, they have the ability to control much of their own destiny on many levels - including occupying new biological spaces within the human host - growing uncontrollably, and eventually killing the host.

Adding to the complexity picture is the astounding pace of technology in biomedicine overall and particularly in cancer. Through the power of advanced technologies, the DNA of cancers is being sequenced, biomarkers of cancer are being explored, "signaling" pathways are under construction, and nanomedicine is developing quickly, to name a few advances. So if knowledge about cancer is accumulating on so many fronts, why was it important to hold a meeting where the intent was to explore how to best engage scientists from physics, mathematics, physical chemistry, and engineering in our national effort to conquer this horrific disease? Are there still problems left to solve that will benefit from these new fields? The answer to the question is a resounding yes. There are seminal questions that represent major barriers in cancer research today that will undoubtedly require new ideas, strategies, and approaches from the physical sciences to solve. In many ways, the more we know - the more complex the whole question of cancer and its control becomes - understanding this complexity will undoubtedly require significant knowledge and expertise from the physical sciences.

Currently cancer research overall does not broadly embrace physics, mathematics, physical chemistry, and critical fields of engineering through transdisciplinary efforts. These areas are often viewed as tangential to cancer research, and training in physics and mathematics is rarely available to career cancer biologists. In this regard, attempting to redirect well-trained cancer experts to achieve the goal of convergence of these fields is likely not a realistic approach.

It is becoming increasingly obvious, as we drill down into the molecular level of cancer, that addressing key basic questions surrounding areas such as energy and energy flows, short-range forces, cellular mechanics, and cell shape and tensegrity, as well as larger questions such as the physics of the metastatic process, is critical to understanding and controlling cancer. Cancer research needs new ideas, deep innovation, and new and unprecedented transdisciplinary teams of scientists to address these and other key questions. We have arrived at a point where understanding and controlling cancer will increasingly depend on the convergence of cancer research with the disciplines that comprise the physical sciences. We believe that the time is at hand to open this new frontier.

The first NCI-sponsored meeting to tackle this complex undertaking, "Integrating and Leveraging the Physical Sciences to Open a New Frontier in Oncology, was held in Washington, D.C., February 26-28, 2008. It was the beginning of a process of working with thought leaders from physics, mathematics, chemistry, nanotechnology, and engineering to achieve this audacious, but achievable, goal.

The meeting was, to say the least, interesting and provocative; participants challenged assumptions and offered innovative ideas and approaches, and many initiated dialogue on how to accomplish the integration of the physical sciences into the "fabric" of cancer research in the most effective manner, through new scientific collaborations.

Through the creation of this Web site, we have attempted to bring together in one place all of the various presentations, discussions, and emerging scientific focus areas that constituted the substance and output of the think tank. The site and meeting report will allow you to visit the very interesting opening presentation by Dr. Paul Davies and further explore the two intense days of keynote presentations, panel discussions, brainstorming sessions, and working group meetings. We encourage you to revisit the sessions and review the graphics for the various activities and the input from the working groups. Finally, we hope that you will visit the Forum noted as a tab at the top of the opening page of the Web site and participate fully in our discussions beyond the meeting.

The meeting was rich with innovative thinking, but a few areas of consensus emerged that are highlighted in the Forum: cancer's complexity; tumor cell evolution; information transfer in cancer; and a selected number of fundamental principles and laws of physics that have significant relevance in cancer. Many other innovative ideas were offered, and some of these should represent new areas of conversation to be opened in the Forum. We encourage you to be bold in expanding on the consensus areas and equally visionary in posing new questions for discussion. We have summarized what we currently see as next steps from the meeting in a separate section on this Web site, but these followup actions will continue to evolve in the next 6-8 weeks. So visit the Web site often to stay engaged and participate with us in opening this new frontier. Our special thanks go to all of our speakers, our facilitators, Robert Mittman and Thomas Benthin (graphics), and most especially to all of you who gave so freely of your time and shared your ideas.

John E. Niederhuber, M.D.
John E. Niederhuber, M.D.
Director
National Cancer Institute
Anna D. Barker, Ph.D.
Anna D. Barker, Ph.D.
Deputy Director
National Cancer Institute

 

Meeting Objectives

Overall: the NCI's goal in these think tanks is to explore research opportunities at the intersection of the physical sciences and cancer biology that will enable a deeper understanding of cancer and inform the development of better approaches to detect, treat and prevent this complex disease.

  • From the perspective of both the physical and biological sciences - to determine the "state of the science" of evolution and evolutionary theory in terms of our current understanding of cancer at all scales.
  • To explore the relationships between current areas of intense focus in cancer research, e.g., genomics, proteomics, molecularly based drug discovery and development, etc., in terms of the role of evolution and evolutionary theory in oncology at all scales.
  • To identify critical questions in cancer evolution that if addressed will enhance our understanding of cancer development and outcomes.
  • For this think tank, to offer guidance on how through leadership, utilization of existing and new research support mechanisms, etc. the NCI can best engage broader communities of physical and biomedical scientist to address key questions in cancer evolution and evolutionary theory applied to cancer.
Outcomes

The conversations that comprise this think tank, including brainstorming sessions, presentations, roundtables and reports from work groups will be captured in a report - and available on an NCI website dedicated to this Physical-Sciences and Frontiers in Oncology Series. In addition, input from the meeting will be utilized to inform new research directions and mechanisms that will hopefully energize and advance this critical field.

 

Agenda


Sunday, July 13
5:00 p.m. - 6:00 p.m. Registration
6:00 p.m. - 7:15 p.m. Reception and Buffet Dinner Salon II
7:30 p.m. - 7:50 p.m. Background for the Meeting
Anna D. Barker, Ph.D.
Deputy Director
National Cancer Institute

Welcome and Introduction of Keynote Presentation
John E. Niederhuber, M.D.
Director
National Cancer Institute
Salon I
7:50 p.m. - 8:50 p.m. Keynote Presentation
The Causes and Prevention of Cancer: Can an Evolutionary Perspective Allow Us to See the Forest and the Trees?
Paul W. Ewald, Ph.D.
Professor and Director, Program on Disease Evolution
University of Louisville
  Questions and Discussion
8:50 p.m. - 9:00 p.m. Think Tank Process Introductions
Anna D. Barker, Ph.D.
Deputy Director
National Cancer Institute
9:00 p.m. - 9:15 p.m. Expectations
Facilitator: Robert J. Mittman, M.S., M.P.P.
Founder/President
Facilitation, Foresight, Strategy
Meeting Facilitator
Monday, July 14
7:00 a.m. - 8:00 a.m. Continental Breakfast
8:00 a.m. - 8:30 a.m.

Welcome
John E. Niederhuber, M.D.
Director
National Cancer Institute

Background for Today's Think Tank
Anna D. Barker, Ph.D.
Deputy Director
National Cancer Institute

Salons I
  Process and Flow for the Think Tank
Facilitator: Robert J. Mittman, M.S., M.P.P.
Founder/President
Facilitation, Foresight, Strategy
Introduction-Keynote Presentation
8:30 a.m. - 10:00 a.m. Evolution and Evolutionary Theory in Cancer; Status of the Field
An Environmental Scan
Group Discussion
Facilitator: Robert J. Mittman, M.S., M.P.P.
Founder/President
Facilitation, Foresight, Strategy
Meeting Facilitator
10:00 a.m. - 10:15 a.m. Break
10:15 a.m. - 10:45 a.m. Keynote Presentation
Evolution and Cancer: Through the Eyes of a Physicist
Robert H. Austin, Ph.D.
Department of Physics
Princeton University
10:45 a.m. - 11:15 a.m. Keynote Presentation
Evolution and Cancer: A Biologist View of the State of the Science
Carlo C. Maley, Ph.D.
Assistant Professor
The Wistar Institute
11:15 a.m. - 12:30 p.m. Group Discussions
Evolution and Evolutionary Theory: What are the Critical Questions and/or Barriers?

Facilitator: Robert J. Mittman, M.S., M.P.P.
Founder/President
Facilitation, Foresight, Strategy
12:30 p.m. - 1:35 p.m. Lunch
1:30 p.m. - 3:00 p.m.

Roundtable Discussion: Exploration of these and Other Critical Questions/Barriers Surrounding Evolution, Evolutionary Theory and Cancer

Roundtable Participants

Paul Davies, Ph.D.
Professor and Director
Beyond Institute

Donald S. Coffey, Ph.D.
Distinguished Professor of Urology
Johns Hopkins University

Raju Kucherlapati, Ph.D.
Scientific Director
Harvard Partners Center for Genetics and Genomics

Brian J. Reid, M.D., Ph.D.
Member, Fred Hutchinson Cancer Research Center
Professor of Medicine, University of Washington

3:00 p.m. - 3:15 p.m. Break
3:15 p.m. - 5:15 p.m.

Evolution and Evolutionary Theory in Cancer - Addressing the Critical Questions (An Integrated Group Conversation)

Group Discussions
Individual Group Facilitation and Reporting
Facilitator: Robert J. Mittman, M.S., M.P.P.
Founder/President
Facilitation, Foresight, Strategy
5:15 p.m. - 5:45 p.m. Quick Hit (Headlines) Report From the Groups
Facilitator: Robert J. Mittman, M.S., M.P.P.
Founder/President
Facilitation, Foresight, Strategy

Plan for Tomorrow

6:30 p.m. Reception and Dinner

Foyer Salon I

Tuesday, July 15
7:00 a.m. - 8:00 a.m. Continental Breakfast
8:00 a.m. - 8:15 a.m. Review of Day 1
Facilitator: Robert J. Mittman, M.S., M.P.P.
Founder/President
Facilitation, Foresight, Strategy
Salon I
8:15 a.m. - 8:45 a.m. Keynote Presentation
Breast Cancer: Would Evolutionary Thinking Change Our Understanding and Management of this Complex Disease?
Larry Norton, M.D.
Deputy Physician-in-Chief for Breast Cancer Programs
Memorial Sloan-Kettering Cancer Center
8:45 a.m. - 10:15 a.m.

Panel: Research and Commentary - Cancer in the Context of Evolution
(Cancer as Viewed by Evolutionists; Development of Interventions - What Could Change? Modeling in the Context of Evolution)

Cell Lineages - Mutations - and "Predisposition" to Cancer
Steven A. Frank, Ph.D.
Professor
University of California at Irvine

Dynamics of Multilevel Selection and Cancer
John W. Pepper, Ph.D.
Assistant Professor
University of Arizona

Applying Evolutionary Principles and Theory to the Development of Interventions for Cancer
Kenneth J. Pienta, M.D.
Professor
The University of Michigan

Evolution and New Models for Cancer Development and Progression: What Will It Take to Inform the Models?
Thomas S. Deisboeck, M.D.
Assistant Professor
Harvard-MIT (Massachussetts General Hospital)

Questions/Discussion

10:15 a.m. - 10:30 a.m. Break
10:30 a.m. - 1:30 p.m. Converging on the Key Areas of Focus*
Group Discussions - Concept Development Groups Input and Recommendations Salon I, Attaché and Ambassador
 

Working Lunch

Concept work groups continue and prepare to report out

1:30 p.m. - 2:45 p.m. Report Outs: Group Consensus Input - Report Format and Direction and Timing Salon I
2:45 p.m. - 3:00 p.m.

Summary and Next Steps
John E. Niederhuber, M.D.
Director
National Cancer Institute

Anna D. Barker, Ph.D.
Deputy Director
National Cancer Institute

 

Readings


  1. Abu-Asab, M., M. Chaouchi, and H. Amri, Evolutionary medicine: A meaningful connection between omics, disease, and treatment. Proteomics Clin Appl, 2008. 2(2): p. 122-134.
  2. Anderson, C. The end of theory: will the data deluge make the scientific method obsolete? Edge 2008; Available from: http://www.edge.org/3rd_culture/anderson08/anderson08_index.html.
  3. Axelrod, R., D.E. Axelrod, and K.J. Pienta, Evolution of cooperation among tumor cells. Proc Natl Acad Sci U S A, 2006. 103(36): p. 13474-9.
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  5. Brash, D.E., et al., Colonization of adjacent stem cell compartments by mutant keratinocytes. Semin Cancer Biol, 2005. 15(2): p. 97-102.
  6. Coffey, D.S., Self-organization, complexity and chaos: the new biology for medicine. Nat Med, 1998. 4(8): p. 882-5.
  7. Coffey, D.S., Similarities of prostate and breast cancer: Evolution, diet, and estrogens. Urology, 2001. 57(4 Suppl 1): p. 31-8.
  8. Deisboeck, T.S., et al., In silico cancer modeling: is it ready for prime time? Nat Clin Pract Oncol, 2009. 6(1): p. 34-42.
  9. Ewald, P.W., Evolutionary medicine and the causes of chronic disease, in Human Evolution, M.P. Muehlenbein, Editor. 2009 anticipated, Cambridge University Press: Cambridge, UK.
  10. Feinberg, A.P., Epigenetics at the epicenter of modern medicine. JAMA, 2008. 299(11): p. 1345-50.
  11. Feinberg, A.P., R. Ohlsson, and S. Henikoff, The epigenetic progenitor origin of human cancer. Nat Rev Genet, 2006. 7(1): p. 21-33.
  12. Fong, J.H., et al., Modeling the evolution of protein domain architectures using maximum parsimony. J Mol Biol, 2007. 366(1): p. 307-15.
  13. Frank, S.A., Dynamics of cancer: incidence, inheritance, and evolution. Princeton series in evolutionary biology. 2007, Princeton, N.J.: Princeton University Press. xi, 378 p.
  14. Frank, S.A. and M.A. Nowak, Cell biology: Developmental predisposition to cancer. Nature, 2003. 422(6931): p. 494.
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  17. Gonzalez-Garcia, I., R.V. Sole, and J. Costa, Metapopulation dynamics and spatial heterogeneity in cancer. Proc Natl Acad Sci U S A, 2002. 99(20): p. 13085-9.
  18. Gupta, G.P. and J. Massague, Cancer metastasis: building a framework. Cell, 2006. 127(4): p. 679-95.
  19. Heng, H.H., Cancer genome sequencing: the challenges ahead. Bioessays, 2007. 29(8): p. 783-94.
  20. Heng, H.H., et al., Stochastic cancer progression driven by non-clonal chromosome aberrations. J Cell Physiol, 2006. 208(2): p. 461-72.
  21. Hinow, P., et al., The DNA binding activity of p53 displays reaction-diffusion kinetics. Biophys J, 2006. 91(1): p. 330-42.
  22. Knudson, A.G., Chasing the cancer demon. Annu Rev Genet, 2000. 34: p. 1-19.
  23. Knudson, A.G., Two genetic hits (more or less) to cancer. Nat Rev Cancer, 2001. 1(2): p. 157-62.
  24. Maley, C.C., et al., Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet, 2006. 38(4): p. 468-73.
  25. Merlo, L.M., et al., Cancer as an evolutionary and ecological process. Nat Rev Cancer, 2006. 6(12): p. 924-35.
  26. Michor, F., Mathematical models of cancer stem cells. J Clin Oncol, 2008. 26(17): p. 2854-61.
  27. Michor, F., et al., Dynamics of chronic myeloid leukaemia. Nature, 2005. 435(7046): p. 1267-70.
  28. Michor, F., Y. Iwasa, and M.A. Nowak, Dynamics of cancer progression. Nat Rev Cancer, 2004. 4(3): p. 197-205.
  29. Nowak, M.A., Evolutionary dynamics : exploring the equations of life. 2006, Cambridge, Mass.: Belknap Press of Harvard University Press. xi, 363 p.
  30. Pawelek, J.M. and A.K. Chakraborty, Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis. Nat Rev Cancer, 2008. 8(5): p. 377-86.
  31. Rubin, H., What keeps cells in tissues behaving normally in the face of myriad mutations? Bioessays, 2006. 28(5): p. 515-24.
  32. Rubin, H., Cell-cell contact interactions conditionally determine suppression and selection of the neoplastic phenotype. Proc Natl Acad Sci U S A, 2008. 105(17): p. 6215-21.
  33. Shibata, D. and S. Tavare, Counting divisions in a human somatic cell tree: how, what and why? Cell Cycle, 2006. 5(6): p. 610-4.
  34. Tarafa, G., et al., Mutational load distribution analysis yields metrics reflecting genetic instability during pancreatic carcinogenesis. Proc Natl Acad Sci U S A, 2008. 105(11): p. 4306-11.
  35. Wang, Z. and T. Deisboeck, Computational modeling of brain tumors: discrete, continuum or hybrid? Scientific Modeling and Simulation, 2008. 15(1): p. 381-393.
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