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

Participant List

Workshop Report

Perspective in Nature Genetics: Characterizing the ecological and evolutionary dynamics of cancer