EVALUATING EVIDENCE FOR THE USE OF PARP INHIBITORS IN CANCERS WITHOUT BRCA1 OR BRCA2 MUTATIONS

Abstract

PARP inhibitors are a class of drugs FDA approved to treat cancers with BRCA1 and BRCA2 mutations. This review focuses on the use of PARP inhibitors in cancers without BRCA1 and BRCA2 mutations and tries to determine how PARP inhibitors can be used to target cancers with DNA repair defects beyond BRCA1 and BRCA2 mutations. There is evidence that SLFN11 may be a biomarker for sensitivity to PARP inhibitors in small cell lung cancer and Ewing sarcoma. There is also evidence that enzalutamide can downregulate genes in homologous recombination pathway to sensitize prostate cancer to PARP inhibitors. However, this evidence has mostly been shown preclinically and the clinical data is not sufficient for treatment of any of these cancer types without BRCA1 or BRCA2 mutations.