The Clinical Challenges, Trials, and Errors of Combatting Poly(ADP-Ribose) Polymerase Inhibitors Resistance.

ABSTRACT:

Abstract

The use of poly(ADP-ribose) polymerase inhibitor (PARPi) exploits synthetic lethality in solid tumors with homologous recombination repair (HRR) defects. Significant clinical benefit has been established in breast and ovarian cancers harboring BRCA1/2 mutations, as well as tumors harboring characteristics of "BRCAness." However, the durability of treatment responses is limited, and emerging data have demonstrated the clinical challenge of PARPi resistance. With the expanding use of PARPi, the significance of PARP therapy in patients pretreated with PARPi remains in need of significant further investigation. Molecular mechanisms contributing to this phenomenon include restoration of HRR function, replication fork stabilization, BRCA1/2 reversion mutations, and epigenetic ch

SUBMITTER: Pham MM 

PROVIDER: S-EPMC9255699 | biostudies-literature | 2021 Nov-Dec 01

REPOSITORIES: biostudies-literature