Cancer models, genomic instability and somatic cellular Darwinian evolution

The biology of cancer is critically reviewed and evidence adduced that its development can be modelled as a somatic cellular Darwinian evolutionary process. The evidence for involvement of genomic instability (GI) is also reviewed. A variety of quasi-mechanistic models of carcinogenesis are reviewed, all based on this somatic Darwinian evolutionary hypothesis; in particular, the multi-stage model of Armitage and Doll (Br. J. Cancer 1954:8;1-12), the two-mutation model of Moolgavkar, Venzon, and Knudson (MVK) (Math. Biosci. 1979:47;55-77), the generalized MVK model of Little (Biometrics 1995:51;1278-1291) and various generalizations of these incorporating effects of GI (Little and Wright Math. Biosci. 2003:183;111-134; Little et al. J. Theoret. Biol. 2008:254;229-238). REVIEWERS: This article was reviewed by RA Gatenby and M Kimmel.