Modeling a continuum of drug-induced persistence during targeted cancer therapy

We introduce a general phenomenological framework for understanding how phenotypic plasticity gives rise to drug persisters. These persisters, often quiescent but which sometimes return to cycling, survive in the presence of targeted therapy and eventually can lead to mutants with true resistance. Our framework builds on recent experimental observations regarding variations between and among single-cell clones and the possible role of the drug itself in enhancing the survival strategy. Predictions of our approach include the existence of an optimum drug concentration as well as an optimum drug holiday schedule to minimize the persistence-based threat.