PARP Inhibitors: Clinical Development, Emerging Differences, and the Current Therapeutic Issues

Overview

Journal Cancer Drug Resist

Date 2022 May 18

PMID 35582575

Authors

Pooja Murthy

Franco Muggia

Affiliations

Soon will be listed here.

Abstract

Following years in development, poly-adenosyl-ribose polymerase (PARP) inhibitors continue to advance the treatment of ovarian and breast cancers, particularly in patients with pathogenic mutations. Differences in clinical trial design have contributed to distinct indications for each of the PARP inhibitors. Toxicity patterns are also emerging that suggest agents differ in their normal tissue tolerance - beyond what might be expected by dose variations and/or exposure to prior treatment. PARP inhibitor resistance is an increasingly relevant issue as the drugs move to the forefront of advanced ovarian/breast cancer treatment, and is an active area of ongoing research. This review examines the PARP inhibitor clinical trials that have led to approved indications in ovarian and breast cancers, PARP inhibitor targets and pharmacological differences between the PARP inhibitors, emerging mechanisms of resistance, and key clinical questions for future development.

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