Chapter 17: Enzymes in the Base Excision Repair Pathway as Targets for Small Molecule Mediated Therapeutics
Despite the advent of precision medicine and an expanding armamentarium of targeted therapies available to oncologists, DNA-damaging chemotherapy and ionizing radiation (IR) remain foundational care standards for the treatment of cancer. The anti-cancer activity of such DNA-damaging therapies relies on the induction and accumulation of cytotoxic lesions, such as DNA strand crosslinks and double-stranded DNA breaks. Yet, many pharmacologically active agents do not induce such cytotoxic lesions directly; rather they induce a broad spectrum of DNA base damages that are generally regarded to beminimally cytotoxic. Efficacy of such agents may be conferred by DNA repair insufficiency in target tissue that may arise due to genetic insufficiency or concomitant pharmacological treatment.