title: PARP inhibitors: A new era of targeted therapy.
abstract: Personalized medicine seeks to utilize targeted therapies with increased selectivity and efficacy in preselected patient cohorts. One such molecularly targeted therapy is enabled by inhibiting the enzyme poly(ADP-ribose) polymerase (PARP) by small molecule inhibitors in tumors which have a defect in the homologous DNA recombination pathway, most characteristically due to BRCA mutations. Olaparib, a highly potent PARP inhibitor, has recently been the approved for ovarian cancer therapy by the FDA and European commission in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with BRCA1 or BRCA2 mutations. Currently, clinical trials with several PARP inhibitors are being conducted to assess the toxicities, the efficacies and the benefit of the drugs as monotherapies or combined with radiation or other chemotherapeutic agents, in ovarian, breast, prostate, rectal, lung, pancreatic, peritoneal, head and neck, brain, squamous cell carcinomas and sarcomas, to list a few. In this review, our focus is to outline the emerging molecular mechanisms, preclinical evidence and clinical applications of PARP inhibitors especially in nonBRCA cancers, and review the combination strategies compatible with PARP inhibitor therapy.
authors.affiliation: Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, United States; Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, United States.
authors.forename: Shifalika
authors.initials: S
authors.lastname: Tangutoori
authors.affiliation: Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, United States.
authors.forename: Paige
authors.initials: P
authors.lastname: Baldwin
authors.affiliation: Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, United States; Department of Radiation Oncology, Harvard Medical School, Boston, MA, United States. Electronic address: s.sridhar@neu.edu.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sridhar
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
keywords: BMN-673; Lynparza; Olaparib; PARP inhibitors; Personalized medicine