title: Defective DNA repair mechanisms in prostate cancer: impact of olaparib.
abstract: The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1) and breast cancer 2 gene (BRCA2) mutations are implicated in the highest risk of prostate cancer (PC) predisposition and aggressiveness. Poly adenosine diphosphate ribose polymerase (PARP) proteins play a key role in DNA repair mechanisms and represent a valid target for new therapies. Olaparib is an oral PARP inhibitor that blocks DNA repair pathway and coupled with BRCA mutated-disease results in tumor cell death. In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. Waiting for randomized phase III trials, olaparib should be considered as a promising treatment option for PC.
authors.affiliation: Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Felice
authors.affiliation: Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tombolini
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, L'Aquila.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marampon
authors.affiliation: Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Musella
authors.affiliation: Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Marchetti
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D010793:Phthalazines / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531550:olaparib
keywords: BRCA; DNA-repair; PARP; castration resistant; metastatic disease; olaparib; prostate cancer