Open Access

REVIEW

Is autophagy induction by PARP inhibitors a target for therapeutic benefit?

AHMED M. ELSHAZLY^1,2, TUONG VI V. NGUYEN¹, DAVID A. GEWIRTZ^1,*

1 Department of Pharmacology and Toxicology, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA, 23298, USA
2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt

* Corresponding Author: DAVID A. GEWIRTZ. Email:

Oncology Research 2022, 30(1), 1-12. https://doi.org/10.32604/or.2022.026459

Received 07 September 2022; Accepted 11 November 2022; Issue published 06 December 2022

Abstract

PARP inhibitors have proven to be effective in conjunction with conventional therapeutics in the treatment of various solid as well as hematologic malignancies, particularly when the tumors are deficient in DNA repair pathways. However, as the case with other chemotherapeutic agents, their effectiveness is often compromised by the development of resistance. PARP inhibitors have consistently been reported to promote autophagy, a process that maintains cellular homeostasis and acts as an energy source by the degradation and reutilization of damaged subcellular organelles and proteins. Autophagy can exhibit different functional properties, the most prominent being cytoprotective. In addition, both cytotoxic and non-protective functions forms have also been identified. In this review, we explore the available literature regarding the different roles of autophagy in response to clinically-used PARP inhibitors, highlighting the possibility of targeting autophagy as an adjuvant therapy to potentially increase the effectiveness of PARP inhibition and to overcome the development of resistance.

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Keywords

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