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Mol Biol Evol. 2019 Oct 23. pii: msz242. doi: 10.1093/molbev/msz242. [Epub ahead of print]

Molecular biology and evolution of cancer: from discovery to action.

Author information

1
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
2
Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
3
Tufts University, Medford, MA, USA.
4
Department of Biology, Emmanuel College, Boston, MA.
5
Department of Anthropology, University of California, Santa Barbara, Santa Barbara CA, USA.
6
Dept. of Biology, University of Massachusetts, Amherst, MA.
7
Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
8
The Jackson Laboratory for Genomic Medicine, Farmington, CT.
9
Cancer Systems Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK and King's College London, London SE11UL, UK.
10
Department of Pathology and Molecular Medicine, School of Medicine, Queen's University, Kingston, ON, Canada K7L 3N6.
11
Ontario Institute of Cancer Research, Toronto, ON, Canada M5G 0A3.
12
Broad Institute, Cambridge, MA.
13
Institute for Genomics and Evolutionary Medicine, and Department of Biology, Temple University, Philadelphia, PA, USA.
14
North Carolina Museum of Natural Sciences, Raleigh, NC, USA.
15
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
16
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA.
17
Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.

Abstract

The progression of cancer is an evolutionary process. During this process, evolving populations of cancer cells encounter restrictive ecological niches within the body, such as the primary tumor, the circulatory system, and diverse metastatic sites. Heterogeneous populations of cancer cells undergo selection for adaptive phenotypes, which shapes molecular genetic variation amid concomitant genetic drift. Cell lineages undergo convergent evolution toward phenotypes known as the hallmarks of cancer that promote cancer initiation, growth, and metastasis. Efforts to prevent or delay cancer evolution-and progression-require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform-and possibly transform-cancer biology in new and meaningful ways. These concepts and tools include comparative research on cancer across diverse species and application of phylogenetic approaches to analyze the evolution of tumor progression and metastasis. Fitness landscapes can be leveraged to describe potential trajectories of cancer evolution, mapping positive selection and neutral evolution of proto-oncogenes, tumor suppressors, and other functional elements. We also highlight current challenges to applying these concepts and propose research areas that, by incorporating these concepts, could identify new therapeutic modes and vulnerabilities in cancer.

PMID:
31642480
DOI:
10.1093/molbev/msz242

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