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Characterizing the ecological and evolutionary dynamics of cancer

Nature Genetics volume 52, pages 759–767 (2020)Cite this article

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Abstract

Tumor initiation and progression are somatic evolutionary processes driven by the accumulation of genetic alterations, some of which confer selective fitness advantages to the host cell. This gene-centric model has shaped the field of cancer biology and advanced understanding of cancer pathophysiology. Importantly, however, each genotype encodes diverse phenotypic traits that permit acclimation to varied microenvironmental conditions. Epigenetic and transcriptional changes also contribute to the heritable phenotypic variation required for evolution. Additionally, interactions between cancer cells and surrounding stromal and immune cells through autonomous and non-autonomous signaling can influence competition for survival. Therefore, a mechanistic understanding of tumor progression must account for evolutionary and ecological dynamics. In this Perspective, we outline technological advances and model systems to characterize tumor progression through space and time. We discuss the importance of unifying experimentation with computational modeling and opportunities to inform cancer control.

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Fig. 1: Schematic illustration of tumor progression from initiation through treatment resistance and metastasis.
Fig. 2: Correlative studies in patient tissue and plasma samples enable investigation of tumor evolution and cellular phenotypes associated with disease progression.
Fig. 3: Schematic overview of experimental cancer models and assays to study cancer gene function and cellular phenotypes.
Fig. 4: Overview of biological processes associated with cancer progression and approaches to characterize them.

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Acknowledgements

This Perspective is based on discussions from a workshop supported by the NCI’s PS-ON. A list of workshop participants and their affiliations is provided in the Supplementary Note.

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Author notes

  1. Ruping Sun

    Present address: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

Authors and Affiliations

  1. Division of Cancer Biology, National Cancer Institute, Rockville, MD, USA

    Nastaran Zahir & Daniel Gallahan

  2. Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA

    Ruping Sun & Christina Curtis

  3. Departments of Radiology and Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Robert A. Gatenby

  4. Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA

    Christina Curtis

  5. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA

    Christina Curtis

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Contributions

N.Z. recorded and synthesized notes from the PS-ON workshop. R.S. drafted an outline of concepts discussed at the workshop. C.C. wrote the manuscript and drafted the figures. N.Z., R.S., D.G. and R.A.G. provided revisions on the manuscript. All authors approved the final manuscript.

Corresponding author

Correspondence to Christina Curtis.

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Competing interests

C.C. is a scientific advisor to GRAIL and reports stock options, as well as consulting for GRAIL and Genentech. N.Z., R.S., D.G. and R.A.G. have no conflicts of interest to report.

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Zahir, N., Sun, R., Gallahan, D. et al. Characterizing the ecological and evolutionary dynamics of cancer. Nat Genet 52, 759–767 (2020). https://doi.org/10.1038/s41588-020-0668-4

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