Targeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials

Abstract

Ionizing radiation is frequently used to treat solid tumors, as it causes DNA damage and kill cancer cells. However, damaged DNA is repaired involving poly-(ADP-ribose) polymerase-1 (PARP-1) causing resistance to radiation therapy. Thus, PARP-1 represents an important target in multiple cancer types, including prostate cancer. PARP is a nuclear enzyme essential for single-strand DNA breaks repair. Inhibiting PARP-1 is lethal in a wide range of cancer cells that lack the homologous recombination repair (HR) pathway. This article provides a concise and simplified overview of the development of PARP inhibitors in the laboratory and their clinical applications. We focused on the use of PARP inhibitors in various cancers, including prostate cancer. We also discussed some of the underlying principles and challenges that may affect the clinical efficacy of PARP inhibitors.

Keywords: BRCA mutations; DNA repair; PARP inhibitors; Synthetic lethality.