Evolutionary Determinants of Cancer

Mel Greaves: Evolutionary Determinants of Cancer

Published OnlineFirst July 20, 2015; DOI: 10.1158/2159-8290.CD-15-0439


Our understanding of cancer is being transformed by exploring clonal diversity,
drug resistance, and causation within an evolutionary framework. The therapeutic
resilience of advanced cancer is a consequence of its character as a complex, dynamic, and adaptive
ecosystem engendering robustness, underpinned by genetic diversity and epigenetic plasticity. The
risk of mutation-driven escape by self-renewing cells is intrinsic to multicellularity but is countered by
multiple restraints, facilitating increasing complexity and longevity of species. But our own species has
disrupted this historical narrative by rapidly escalating intrinsic risk. Evolutionary principles illuminate
these challenges and provide new avenues to explore for more effective control.
Significance: Lifetime risk of cancer now approximates to 50% in Western societies. And, despite many
advances, the outcome for patients with disseminated disease remains poor, with drug resistance the
norm. An evolutionary perspective may provide a clearer understanding of how cancer clones develop
robustness and why, for us as a species, risk is now off the scale. And, perhaps, of what we might best
do to achieve more effective control. Cancer Discov; 5(8); 1–15. © 2015 AACR.

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