Evolutionary Dynamics of Cancer
Executive Summary
Workshop Concept and Goals
Dobzhansky famously stated that “nothing in biology makes sense except in the light of evolution.” Since then, others have stated “nothing in evolution makes sense except in the light of genetics” and “nothing in evolution makes sense except in the light of ecology.”
This workshop explored the quantitative expression of these complex, multi-scalar dynamics through application of fitness landscapes that link genotypes and phenotypes to reproductive success (fitness) within the context of local environmental conditions.
Accumulating mutations or changes in pattern of gene expression provide the mechanisms of inheritance for evolution. However, each genotype encodes a reaction norm of often-diverse phenotypic traits that permit acclimation to some changes in environmental conditions. Furthermore, evolutionary convergence can allow many different genotypes to specify a single common phenotype and the fitness of any phenotype depends entirely on its environmental (ecological) context.
For cancer cells, their local microenvironment, and its associated Darwinian selection forces, can vary dramatically over space and time as a function of changes in blood flow and host response or iatrogenic perturbations in the form of therapy. Finally, cancer cells can evolve niche construction adaptive strategies to generate local environmental conditions that maximize their fitness creating both evolutionary (population) and ecological (the persisting niche) modes of inheritance.
By quantitatively framing these complex dynamics, fitness landscapes can provide novel insights into the multi-scalar dynamics in cancer biology and treatment including cellular plasticity, tumor-host interactions, and resistance to therapy.
This workshop highlighted areas of study in evolutionary dynamics of cancer, identified emerging areas of emphasis, assessed the state of the field, and discussed future opportunities and how the field can be moved forward.
Topics for Focused Discussion During Workshop Sessions
Session 1. Initiation and Early Disease
Examined on in situ cancers in which the cells evolve within ducts or on mucosal surface. Discussion topics focused on cell-cell competition that leads to evolution of cellular hallmarks like resistance to growth inhibition, independence of growth factors, resistance to cell death, acquisition of limitless replication, increased mutation rate, etc.
Session 2. Progression and Metastases
Explored tissue-level dynamics that follows transition from in situ to invasive cancers.
Discussion topics focused on macroscopic tumor-host eco-evolutionary interactions like niche construction (e.g., angiogenesis and perhaps chronic inflammation), immune evasion, and colonization of distant sites (i.e., adapting to “foreign tissue adaptive landscapes)
Session 3. Resistance to Cancer Therapy
Discussion topics focused on adaptive strategies that permit survival and proliferation following iatrogenic perturbations.
Agenda
Evolutionary Dynamics of Cancer
NCI Division of Cancer Biology Strategic Workshop
August 9-10, 2018
National Cancer Institute Shady Grove Campus
Rockville, Maryland
Workshop Co-Chairs: Robert A. Gatenby, MD, & Christina Curtis, PhD, MSc
Thursday, August 9, 2018 | |
9:00 am – 9:30 am | Welcome and Introductions - Room 2W910/912
Robert A. Gatenby, MD, Moffitt Cancer Center |
9:30 am – 10:30 am |
Keynote Opening Talks |
9:30 am – 10:00 am | Darwinian Dynamics in Cancer Biology and Therapy Robert A. Gatenby, MD, Moffitt Cancer Center |
10:00 am – 10:30 am | Towards Quantifying and Forecasting Human Tumor Progression Christina Curtis, PhD, MSc, Stanford University |
10:30 am – 1:00 pm | Session 1: Initiation and Early Disease
Session Chair: Carlo Maley, PhD, Arizona State University |
10:30 am – 10:35 am | Opening by Session Chair |
10:35 am – 11:00 am | Evolutionary Dynamics of Neoplastic Progression Carlo Maley, PhD, Arizona State University |
11:00 am – 11:25 am | Cancer is a Disease of Epigenetic Stochasticity Andrew P. Feinberg, MD, MPH, Johns Hopkins University |
11:25 am – 11:40 am | Break |
11:40 am – 12:05 pm | Virus Density and Infectious Causation of Cancers Paul W. Ewald, PhD, University of Louisville |
12:05 pm – 12:30 pm | Highly Multiplex 2D and 3D Optical Imaging Methods for Examining Tumor Development and Organization Ronald Germain, MD, PhD, National Institute of Allergy and Infectious Diseases |
12:30 pm – 1:00 pm | Discussion |
1:00 p.m. – 1:45 p.m. | Lunch (on own) |
1:45 pm – 4:20 pm | Session 2: Progression and Metastasis
Session Chair: Christine Iacobuzio-Donahue, MD, PhD, Memorial Sloan Kettering Cancer Center |
1:45 pm – 1:50 pm | Opening by Session Chair |
1:50 pm – 2:15 pm | Evolutionary Dynamics of Pancreatic Cancer Christine Iacobuzio-Donahue, MD, PhD, Memorial Sloan Kettering Cancer Center |
2:15 pm – 2:40 pm | Therapeutic Eutrophication and its Implications for Cancer Progression Kenneth J. Pienta, MD, Johns Hopkins University |
2:40 pm – 3:00 pm | Break |
3:00 pm – 3:25 pm | Tracing the Evolution of Metastasis with Hypermutable DNA Kamila Naxerova, PhD, Massachusetts General Hospital |
3:25 pm – 3:50 pm | Evolved Resistance and Vulnerability to Invasion Günter Wagner, PhD, Yale University |
3:50 pm – 4:20 pm | Discussion |
4:20 pm – 4:45 pm | Recap and Preview of Day 2
Robert A. Gatenby, MD, Moffitt Cancer Center |
4:45 pm | Adjourn Day 1 |
4:45 pm | Shuttle service to Sheraton Rockville Hotel |
6:00 pm | Group dinner (on your own) Thai Farm, 800 King Farm Blvd, Suite 125 |
Agenda: Friday August 10, 2018 | |
8:00 am | Shuttle Departs Sheraton Rockville Hotel for NCI Shady Grove |
8:30 am – 9:00 am | Security at NCI Shady Grove |
9:00 am – 9:25 am | Day 2 Opening Remarks - Room 2W910/912
Robert A. Gatenby, MD, Moffitt Cancer Center |
9:25 am – 12:00 pm | Session 3: Resistance to Cancer Therapy
Session Chair: Dan Landau, MD, PhD, Weill Cornell/ NY Genome Center |
9:25 am – 9:30 am | Opening by Session Chair |
9:30 am – 9:55 am | Genotype-fitness Maps of EGFR Mutant Lung Adenocarcinoma Chart the Evolutionary Landscape of Resistance and Combination Therapy Optimization Dan Landau, MD, PhD, Weill Cornell/ NY Genome Center |
9:55 am – 10:20 am | Targeting Collateral Sensitivity in Cancer Michael T. Hemann, PhD, Massachusetts Institute of Technology |
10:20 am – 10:40 am | Break |
10:40 am – 11:05 am | Personalized Adaptive Therapies for Metastatic Melanoma Alexander (Sandy) Anderson, PhD, Moffitt Cancer Center |
11:05 am – 11:30 am | Genetic Instability and Dynamic Precision Medicine of Cancer Robert A Beckman, MD, Georgetown University Medical Center |
11:30 am – 12:00 pm | Discussion |
12:00 pm – 12:45 pm | Lunch (on own) |
12:45 pm – 2:00 pm | Workshop Outcomes, Next Steps, White Paper Planning
Group discussion led by: |
2:00 pm – 2:15 pm | Closing Remarks
Robert A. Gatenby, MD, Moffitt Cancer Center |
2:15 pm | Adjourn |
Participant List
First Name |
Last Name |
Degree |
Institution |
Alexander (Sandy) |
Anderson |
PhD |
Moffitt Cancer Center |
Victoria |
Aranda |
PhD |
Nature Publishing Group |
Robert A. |
Beckman |
MD |
Georgetown University Medical Center |
Jennifer |
Couch |
PhD |
NCI |
Christina |
Curtis |
PhD, MSc |
Stanford University |
Paul W. |
Ewald |
PhD |
University of Louisville |
Andrew P. |
Feinberg |
MD, MPH |
Johns Hopkins University |
Dan |
Gallahan |
PhD |
NCI |
Robert |
Gatenby |
MD |
Moffitt Cancer Center |
Ronald |
Germain |
MD, PhD |
NIAID |
Michael T. |
Hemann |
PhD |
Massachusetts Institute of Technology |
Shannon |
Hughes |
PhD |
NCI |
Christine |
Iacobuzio-Donahue |
MD, PhD |
MSKCC |
Dan |
Landau |
MD, PhD |
Weill Cornell/NY Genome Center |
Carlo |
Maley |
PhD |
Arizona State University |
Kamila |
Naxerova |
PhD |
Massachusetts General Hospital |
Kenneth J. |
Pienta |
MD |
Johns Hopkins University |
Dinah |
Singer |
PhD |
NCI |
Ruping |
Sun |
PhD |
Stanford University |
Gunter |
Wagner |
PhD |
Yale University |
Nastaran |
Zahir |
PhD |
NCI |
Workshop Report
Perspective in Nature Genetics: Characterizing the ecological and evolutionary dynamics of cancer