Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents

Abstract

Cancers with wild-type BRCA, homologous recombination proficiency, or de novo or acquired resistance to PARP inhibition represent a growing population of patients who may benefit from combinatorial PARP inhibitor strategies. We review targeted inhibitors of angiogenesis, epigenetic regulators, and PI3K, MAPK, and other cellular signaling pathways as inducers of homologous recombination deficiency, providing support for the use of PARP inhibitors in contexts not previously considered susceptible to PARP inhibition.

Keywords: AKT pathway; AXL inhibition; Angiogenesis; BET inhibition; GAS6; HDAC inhibition; Hsp90 inhibition; MAPK pathway; MEK inhibition; PI3K; mTOR.