Mechanisms of Selection on Cancer-Causing Mutations

The mainstream thinking in the somatic evolution of cancer is mainly mutation centred. In contrast, evolutionary thinking showing that selection rather than mutation is rate limiting in cancers is an upcoming realization. But so far there are little insights into how selection works on the cancer causing mutations in the context of the tissue microenvironment. A cancer causing mutant also causes one or more disruptions of normal cellular metabolism. Therefore the mutant is unlikely to get selected in competition with normal cells. However, under specific contexts, when the normal adult stem cell dynamics is altered, the mutant is likely to get a selective advantage and thereby outgrow normal cells. We suggest a battery of hypotheses about how context dependent selection is likely to act at the cellular and molecular level. We also weigh the hypotheses against available evidence and suggest a line of experiments that can test the hypotheses.