Leveraging Epigenetics to Enhance the Cellular Response to Chemotherapies and Improve Tumor Immunogenicity

Cancer chemotherapeutic drugs have greatly advanced our ability to successfully treat a variety of human malignancies. The different forms of stress produced by these agents in cancer cells result in both cell autonomous and cell nonautonomous effects. Desirable cell autonomous effects include reduced proliferative potential, cellular senescence, and cell death. More recently recognized cell nonautonomous effects, usually in the form of stimulating an antitumor immune response, have significant roles in therapeutic efficiency for a select number of chemotherapies. Unfortunately, the success of these therapeutics is not universal as not all tumors respond to treatment, and those that do respond will frequently relapse into therapy-resistant disease. Numerous strategies have been developed to sensitize tumors toward chemotherapies as a means to either improve initial responses, or serve as a secondary treatment strategy for therapy-resistant disease. Recently, targeting epigenetic regulators has emerged as a viable method of sensitizing tumors to the effects of chemotherapies, many of which are cytotoxic. In this review, we summarize these strategies and propose a path for future progress.