Episensitization: A New Word for a New Concept

Abstract The purpose of this chapter is to define and examine the treatment strategy of “episensitization,” or the ability to sensitize cancer cells to subsequent therapy by resetting the epigenetic infrastructure of the tumor. One important facet is resensitization by epigenetic mechanisms, which challenges the assumption in oncology that the reuse of previously tried and failed therapies, is a clinically pointless endeavor. Epigenetic changes are reversible and the effect of epigenetic modulation on gene expression and the tumor microenvironment may mediate a return to a baseline state of treatment susceptibility. Episensitization is a novel and highly relevant treatment strategy both as an antidote to the practice of permanently switching to different drugs at each line of therapy, which rapidly exhausts remaining available treatment options, and as a blueprint to substantially prolong overall survival. Accordingly, several epigenetic agents including decitabine, vorinostat, entinostat, 5-azacitidine, oncolytic viruses, and RRx-001 are highlighted in this chapter.