PARP Inhibitor Resistance Mechanisms and Implications for Post-Progression Combination Therapies

Elizabeth K Lee; Ursula A Matulonis

doi:10.3390/cancers12082054

PARP Inhibitor Resistance Mechanisms and Implications for Post-Progression Combination Therapies

Cancers (Basel). 2020 Jul 25;12(8):2054. doi: 10.3390/cancers12082054.

Authors

Elizabeth K Lee¹, Ursula A Matulonis^{1

2}

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215-5450, USA.
² Division of Gynecologic Oncology, Dana-Farber Cancer Institute, Boston, MA 02215-5450, USA.

Abstract

The use of PARP inhibitors (PARPi) is growing widely as FDA approvals have shifted its use from the recurrence setting to the frontline setting. In parallel, the population developing PARPi resistance is increasing. Here we review the role of PARP, DNA damage repair, and synthetic lethality. We discuss mechanisms of resistance to PARP inhibition and how this informs on novel combinations to re-sensitize cancer cells to PARPi.

Keywords: BRCA; DNA damage repair; PARP inhibitor; PARP inhibitor resistance; homologous recombination; ovarian cancer; replication fork.

Publication types

Review