Mechanism of PARP inhibitor resistance and potential overcoming strategies

Xiaoyu Fu; Ping Li; Qi Zhou; Ruyuan He; Guannan Wang; Shiya Zhu; Amir Bagheri; Gary Kupfer; Huadong Pei; Juanjuan Li

doi:10.1016/j.gendis.2023.02.014

Mechanism of PARP inhibitor resistance and potential overcoming strategies

Genes Dis. 2023 Mar 24;11(1):306-320. doi: 10.1016/j.gendis.2023.02.014. eCollection 2024 Jan.

Authors

Xiaoyu Fu^{1

2}, Ping Li³, Qi Zhou^{1

3}, Ruyuan He⁴, Guannan Wang¹, Shiya Zhu¹, Amir Bagheri¹, Gary Kupfer¹, Huadong Pei¹, Juanjuan Li²

Affiliations

¹ Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
² Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
³ Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
⁴ Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

Abstract

PARP inhibitors (PARPi) are a kind of cancer therapy that targets poly (ADP-ribose) polymerase. PARPi is the first clinically approved drug to exert synthetic lethality by obstructing the DNA single-strand break repair process. Despite the significant therapeutic effect in patients with homologous recombination (HR) repair deficiency, innate and acquired resistance to PARPi is a main challenge in the clinic. In this review, we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance, aiming at extending PARPi application and improving patient outcomes.

Keywords: Drug resistance; Homologous recombination; PARP; PARP inhibitor; Poly (ADP-ribose) polymerase.

Publication types

Review