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Applying Evolutionary Biology Strategies to Cancer Research

Overview | Executive Summary | Agenda

Overview

meeting report

Download Workshop Executive Summary, Agenda, and Participants List

NCI Physical Sciences-Oncology Centers (PS-OC) Strategic Workshop

May 21, 2012

Bethesda North Marriott Hotel & Conference Center
North Bethesda, Maryland

Office of Physical Sciences-Oncology
National Cancer Institute
National Institutes of Health
U.S. Department of Health and Human Services

Executive Summary

The National Cancer Institute (NCI) Office of Physical Sciences – Oncology (OPSO) launched the Physical Sciences – Oncology Centers (PS-OC) Program in 2009 to advance our understanding of cancer by bringing novel “physical sciences perspectives” to cancer from teams of physical scientists and cancer researchers working closely together. In May 2012, the OPSO convened a series of two workshops to reflect on progress made in the area of ‘evolution and evolutionary theory of cancer’, a major focus of the PS-OC Program, and identify additional aspects and problems in cancer research that would benefit from more scientific efforts in this area. The first Strategic Workshop in the series, “Applying Evolutionary Biology Strategies to Cancer Research”, aimed to bring physical sciences perspectives and approaches from evolution and evolutionary theory to enable a deeper understanding of cancer and inform better approaches to detect, treat, and prevent this complex disease.

The premise of this workshop was that cancer, as viewed from a physical sciences perspective, is considered an evolving complex adaptive system. Application of physical sciences approaches from evolutionary biology can further our understanding of the complex heterogeneity of cancer within adaptive landscapes. By examining all length scales, from subcellular to ecosystem, the presenters reinforced the need for advancing technologies to provide new knowledge to understand potential underlying evolutionary principles operating in cancer. Roundtable discussions, consisting of experts from evolutionary biology, physical sciences, and oncology, identified recent advances in the field and big questions in cancer research that would benefit from physical sciences approaches in evolutionary biology.

Key findings and ideas generated by the presentations and discussions included:

Continue to apply advancing technologies and models from evolutionary biology to understand cancer dynamics

Deep digital genomic sequencing, novel microfluidic devices, and game theory models are proving useful for understanding the clonal evolution of tumors, the origin and dynamics of cellular heterogeneity, and the development of resistance to both chemotherapy and radiation therapy. New evolutionary principles derived from these data can serve as a framework for creating quantitative models to understand and predict the dynamics of cancer evolution. For example, experiments using engineered microhabitats indicate that ‘selection occurs faster in small populations than a large one’ and may provide insights into the impact of heterogeneity in tumors. Future advances should focus on developing evolutionary models to help identify evolutionary nodes or bottlenecks and compile comprehensive cancer-related data.

Understanding and targeting the evolutionary strategy in cancer

Several examples of evolutionary strategies in microbiology and ecology (e.g., bacteria, biofilms, and predator-prey games) may be applicable to gain a better understanding of cancer progression and therapeutic response. In single bacterium, evidence suggests that selective pressure (e.g., antibiotics) can trigger mutations in specific hotspots related to DNA repair to increase the overall rate of mutagenesis and increase the potential to evolve. Within biofilms, bacterial subclones evolve as a population to maximize productivity of the entire biofilm, not necessarily the individual clone. In ecology, predator-prey evolutionary strategies are dependent on the evolution of the environment as well as the species. Preliminary evidence indicates similar evolutionary strategies in cancer, such as the observation that cancer cells migrate into higher concentrations of doxorubicin during evolution into a drug resistance phenotype. Cancer research should focus on using physical sciences approaches in evolutionary biology to identify potential evolutionary strategies at all length scales that can be used to target or predict the evolutionary responses of cancer cells to therapeutics.

 

Agenda

Meeting Objectives

The NCI’s goal in this strategic workshop is to explore the research opportunities at the intersection of the physical sciences and cancer biology by bringing physical sciences perspectives from evolution and evolutionary theory to enable a deeper understanding of cancer and inform better approaches to detect, treat, and prevent this complex disease.

From the perspective of both the physical and biological sciences, the strategic workshop aims are to:

  • Determine the “state of science” of evolution and evolutionary theory in terms of our current understanding of cancer at all length and time scales.
  • Identify specific critical questions in cancer research that can be addressed by looking at cancer as a complex adaptive system using an evolutionary perspective and if explained will enhance our understanding of cancer development, progression, and metastasis.
  • Identify new tools and advancing technologies from evolutionary biology and ecology that can provide new insights in the control of cancer.
  • Offer guidance on how, through leadership and utilization of existing and new research support mechanisms, the NCI can best engage the broader communities of evolutionary biologists and theorists to address key questions in cancer.

Outcomes

The conversations that comprise this strategic workshop, including brainstorming sessions, presentations, and roundtable discussions will be captured in a report that will be available on the NCI Office of Physical Sciences – Oncology website. In addition, input from the meeting will be used to inform new research directions and mechanisms that will hopefully energize and advance this critical field.

Synopsis

Cancer, as viewed by a physical sciences perspective, is considered a complex adaptive system that is most appropriately studied in the context of evolution and evolutionary theory. Tools from evolution and evolutionary theory, such as game theory, have been employed to further our understanding of the complex heterogeneity of cancer within the adaptive landscapes of tissue ecosystems. A major foundational aspect of this area includes experimentation and theoretical models that support the development of an evolutionary construct to understand, predict and control the cancer process. These constructs include a combination of “omics” data and physical science platforms for evaluating and testing robust theoretical constructs. The mission of NCI’s Office of Physical Sciences-Oncology is to explore new and innovative approaches to better understand and control cancer by enabling the convergence of the physical sciences with cancer biology. To determine the “state of science” in looking at cancer from an evolutionary perspective and explore new areas for advancement, the NCI Office of Physical Sciences – Oncology will convene a meeting of experts from multiple disciplines, including evolutionary biology, physical sciences, and cancer biology, at this strategic workshop to identify key questions and approaches that could open new avenues in cancer research.

8:00 a.m. - 8:20 a.m. Opening Remarks and Introductions
Nicole M. Moore, Sc.D.
Office of Physical Sciences-Oncology
Center for Strategic Scientific Initiatives
National Cancer Institute, NIH
8:20 a.m. - 9:00 a.m. Introductory Keynote Presentation: Applying Physical Sciences Perspectives
From Evolutionary Biology to Solving Challenging Cancer Questions
Elaine R. Mardis, Ph.D.
Co-director
The Genome Institute
Washington University School of Medicine
9:00 a.m. - 9:45 a.m. Panel: Applying Evolutionary Biology Strategies to Enhance Our Understanding of Cancer Initiation, Progression, and Resistance (15 minutes per speaker)

Robert Austin, Ph.D.
Professor
Department of Physics
Princeton University

Susan Rosenberg, Ph.D.
Ben F. Love Chair in Cancer Research
Professor
Departments of Molecular and Human Genetics, Biochemistry and Molecular Biology, and Molecular Virology and Microbiology
Baylor College of Medicine

Andrew Feinberg, M.D., M.P.H.
Professor
Gilman Scholar and King Fahd Professor of Medicine, Molecular Biology and
Genetics, and Oncology, and Biostatistics
Director
Center for Epigenetics
Institute for Basic Biomedical Sciences
Johns Hopkins University School of Medicine

Elaine R. Mardis, Ph.D.*
Co-director
The Genome Institute
Washington University School of Medicine
9:45 a.m. - 10:15 a.m. Q&A and Discussion with Panel
Moderator: Robert A. Gatenby, M.D.
Chair, Radiology
H. Lee Moffitt Cancer Center
10:15 a.m. - 10:35 a.m. Break
10:35 a.m. - 11:10 a.m. Keynote Presentation: An Evolutionary Biologist’s Perspective on Cancer
Joel S. Brown, Ph.D.
Professor of Biology
Department of Biological Sciences
University of Illinois at Chicago
11:10 a.m. - 11:40 a.m. Panel: An Evolutionary Biologist’s Perspective on Complex Ecologies and
Adaptive Systems (15 minutes per speaker)

Paul W. Ewald,
Ph.D. Professor of Biology
University of Louisville

Vaughn S. Cooper, Ph.D.
Associate Professor of Microbiology and Genetics Department of Molecular, Cellular, and Biomedical Sciences University of New Hampshire

Joel S. Brown, Ph.D.1
Professor of Biology
Department of Biological Sciences
University of Illinois at Chicago
11:40 a.m. - 12:10 a.m. Q&A and Discussion With Panel
Moderator: Franziska Michor, Ph.D.
Associate Professor
Dana-Farber Cancer Institute
Harvard School of Public Health
12:10 a.m. - 12:40 p.m. Lunch Break
12:40 p.m. - 1:20 p.m. Roundtable Discussion:
  • Identify two areas where we have made progress in cancer using physical sciences and evolutionary theory approaches.
  • Identify two areas on which to focus in future research using physical sciences and evolutionary theory approaches to understanding cancer.
1:20 p.m. - 1:40 p.m. Report Out From Roundtables
1:40 p.m. - 1:55 p.m. Break
1:55 p.m. - 2:25 p.m. Clinical Perspective: The Ecology of a Tumor
Robert A. Gatenby, M.D.
Chair, Radiology
H. Lee Moffitt Cancer Center
2:25 p.m. - 2:55 p.m. Keynote Presentation: The Ecosystem of Cancer
Larry Norton, M.D.
Deputy Physician in Chief
Breast Cancer Programs
Memorial-Sloan Kettering Cancer Center
2:55 p.m. - 3:25 p.m. Q&A Discussion With Speakers
3:25 p.m. - 3:45 p.m. Break
3:45 p.m. - 4:30 p.m. Roundtable Discussion: Identify “Big” questions in cancer that could be solved using perspectives and tools from evolution or evolutionary theory.
4:30 p.m. - 5:00 p.m. Report Out From Roundtables
5:00 p.m. - 5:10 p.m. Concluding Remarks
Nicole M. Moore, Sc.D.
Office of Physical Sciences-Oncology Center for Strategic Scientific Initiatives National Cancer Institute, NIH