Defective DNA repair mechanisms in prostate cancer: impact of olaparib.

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.

Drug design, development and therapy. 2017 Mar 01*** epublish ***

Francesca De Felice, Vincenzo Tombolini, Francesco Marampon, Angela Musella, Claudia Marchetti

Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome., Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L'Aquila, L'Aquila., Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Rome, Italy.