Adaptive Control of Tumor Growth.

Abstract

Cancer treatment optimizations select the most optimum combinations of drugs, sequencing schedules, and appropriate doses that would limit toxicity and yield an improved patient quality of life. However, these optimizations often lack an adequate consideration of cancer's near-infinite potential for evolutionary adaptation to therapeutic interventions. Adapting cancer therapy based on monitored tumor burden and clonal composition is an intuitively sound approach to the treatment of cancer as an inherently complex and adaptive system. The adaptation would be driven by clinical outcome setpoints embodying the aims to thwart therapeutic resistance and maintain a long-term management of the disease or even a cure. However, given the nonlinear, stochastic dynamics of tumor response to therapeutic interventions, adaptive therapeutic strategies may at least need a one-step-ahead prediction of tumor burden to maintain their control over tumor growth dynamics. The article explores the feasibility of adaptive cancer treatment driven by tumor state feedback assuming cell adaptive fitness to be the underlying source of phenotypic plasticity and pathway entropy as a biomarker of tumor growth trajectory. The exploration is undertaken using deterministic and stochastic models of tumor growth dynamics.