Towards Inverse Modeling of Intratumoral Heterogeneity

Development of resistance limits efficiency of present anticancer therapies and preventing it remains big challenge in cancer research. It is accepted, at intuitive level, that the resistance emerges as a consequence of cancer cells heterogeneity at molecular, genetic and cellular levels. At the same time, population heterogeneity stands as one of fundamental prerequisite of evolutionary theory, which was accepted long time ago as an instructive conceptual framework to understand cancer behavior. Produced by many sources, tumor heterogeneity is extremely complex time dependent statistical characteristics which may be quantified by the measures defined in many different ways, most of them coming from statistical mechanics. While genetic intratumor diversity is well accepted as necessary prerequisite of evolution, the role of non-genetic intratumor diversity in cancer progression is not yet satisfactorily explained. In the paper we present a formal framework to analyze intratumor heterogeneity respecting evolutionary causation of cancer. The approach is based on the concept of master equation, successfully applied in the domain of statistical physics.