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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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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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.
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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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DOI: https://doi.org/10.1038/s41588-020-0668-4
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