title: Predictors and Modulators of Synthetic Lethality: An Update on PARP Inhibitors and Personalized Medicine.
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.
authors.affiliation: Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Murata
authors.affiliation: Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Finch
authors.affiliation: Department of Otorhinolaryngology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Loredana
authors.initials: L
authors.lastname: Campo
authors.affiliation: Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Eun-Kyoung
authors.identifier: 0000-0002-0467-3080
authors.initials: EK
authors.lastname: Breuer
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D005060:Europe; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010793:Phthalazines / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000737:chemistry*; D057285:Precision Medicine / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D014408:Biomarkers, Tumor; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531550:olaparib