Update on PARP inhibitor therapy for solid tumors

Abstract

Poly (ADP-ribose) polymerases (PARPs) play an important role in DNA damage repair. They are primarily involved in base excision repair in single strand breaks. So far, the clinical trial results are very promising in breast and ovarian cancer with deleterious germline BRCA1 and BRCA2 mutations, and their use is expanding to include other solid tumors with homologous recombination (HR) repair defect. Studies suggest a correlation between tumor sensitivity to platinums and response to PARP inhibitors (PARPi) in women with ovarian cancer. The hypothesis is that by interfering with DNA repair, PARPi sensitize cells to DNA-damaging chemotherapies and radiation therapy. This article provides an overview of clinical trial results obtained with PARPi in the treatment of breast, ovarian, prostate, gastric, pancreatic, and lung cancers. In addition, we review resistance mechanisms to PARPi, toxicities of PARPi, and potential treatment combinations with PARPi.