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PARP inhibition: A promising therapeutic target in ovarian cancer.

2015; Cellular and Molecular Biology Association; Volume: 61; Issue: 5 Linguagem: Inglês

10.14715/cmb/2015.61.6.8

1165-158X

Angela Musella, Cláudia Marchetti, Maria Luisa Gasparri, Laura Salerno, Assunta Casorelli, Lavinia Domenici, Ludovica Imperiale, Ilary Ruscito, Talha Abdul Halim, Innocenza Palaia, Violante Di Donato, Francesco Pecorini, Marco Monti, Ludovico Muzii, Pierluigi Benedetti Panici,

Cell death mechanisms and regulation

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers.Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery.Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival.The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers.Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth.PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair.PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction.A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers.This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.