SOMATIC EVOLUTION OF CANCER

Human carcinogenesis may be thought of as Darwinian evolution of cells within the body (somatic evolution). As such, it may be modeled using evolutionary game theory. Winners in this game proliferate while losers become extinct. Here evolutionary dynamics are proposed that model the rate of somatic evolution. The speed at which somatic evolution proceeds determines whether a clinically significant cancer will emerge in the lifetime of the individual. The underlying model has an associated adaptive landscape that illustrates the evolutionary potential of cells due to the selection forces and microenvironment. Normal cells have a novel adaptive landscape that permits both coexistence and invasion of mutant phenotypes. A mutant cellular population does not initially form a malignancy because of constraints resulting in limited growth and nonlethal coexistence. However this coexistence deforms the local adaptive landscape resulting in the potential for evolution to drive the mutant cells to an unoccupied fitness peak resulting in an evasive cancer. There are two factors that determine this evolutionary potential. The first factor involves a relaxation of proliferation constraints and the second involves an increase in nutrients thereby removing a barrier allowing the mutant cells to climb to an adaptive peak. One unfortunate consequence of the cancer reaching this peak is that it starts producing acid that further contributes to the demise of the normal cells.