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BioMed Research International
Volume 2016 (2016), Article ID 2346585, 12 pages
http://dx.doi.org/10.1155/2016/2346585
Review Article

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

1Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
2Department of Otorhinolaryngology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

Received 9 June 2016; Accepted 28 July 2016

Academic Editor: David C. Pauza

Copyright © 2016 Stephen Murata et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.