Predictors and Modulators of Synthetic Lethality: An Update on PARP Inhibitors and Personalized Medicine.

Publication/Presentation Date

1-1-2016

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors have proven to be successful agents in inducing synthetic lethality in several malignancies. Several PARP inhibitors have reached clinical trial testing for treatment in different cancers, and, recently, Olaparib (AZD2281) has gained both United States Food and Drug Administration (USFDA) and the European Commission (EC) approval for use in BRCA-mutated advanced ovarian cancer treatment. The need to identify biomarkers, their interactions in DNA damage repair pathways, and their potential utility in identifying patients who are candidates for PARP inhibitor treatment is well recognized. In this review, we detail many of the biomarkers that have been investigated for their ability to predict both PARP inhibitor sensitivity and resistance in preclinical studies as well as the results of several clinical trials that have tested the safety and efficacy of different PARP inhibitor agents in BRCA and non-BRCA-mutated cancers.

Volume

2016

First Page

2346585

Last Page

2346585

ISSN

2314-6141

Disciplines

Medicine and Health Sciences

PubMedID

27642590

Department(s)

Fellows and Residents

Document Type

Article

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