Update on Combination Strategies of PARP Inhibitors.

Abstract

The application of PARP inhibitors has revolutionized cancer treatment and has achieved significant advancements, particularly with regard to tumors with defects in genes involved in homologous recombination repair (HRR) processes, such as BRCA1 and BRCA2. Despite the promising outcomes of PARP inhibitors, certain limitations and challenges still exist, including acquired drug resistance, severe side effects, and limited therapeutic benefits for patients without homologous recombination deficiency (HRD). Various combinations involving PARP inhibitors have been developed to overcome these limitations. Among these, combinations with immune checkpoint inhibitors, antiangiogenic agents, and various small-molecule inhibitors are well-studied strategies that show great potential for optimizing the efficacy of PARP inhibitors, overcoming resistance mechanisms, and expanding target populations. However, the efficiency and overlapping toxicity of these combination strategies for cancers vary among studies, thereby limiting their use. In this review, we describe the mechanisms and limitations of PARP inhibitors to better understand the mechanisms of combination treatments. Furthermore, we have summarized recent studies on the combination of PARP inhibitors with a range of medications and discussed their clinical efficacy. The objective of this review is to enhance the comprehensiveness of information pertaining to this topic.