Genetic instability is one part of the oncogenic process. Gene mutations involved in DNA repair mechanisms can promote this genetic instability and participate in oncogenesis and metastatic progression. In prostate cancer, DNA repair abnormalities mainly correspond to somatic or constitutional mutations of the BRCA2 and ATM genes. Therapeutic management of metastatic castration-resistant prostate cancer (mCRPC) is currently based on new hormonal therapies (abiraterone, enzalutamide) and taxane-type chemotherapy (docetaxel or cabazitaxel). Preliminary data tend to indicate a specific activity of agents causing DNA breaks (platinum salts) and PARP inhibitors in patients with these DNA repair abnormalities. The frequency of DNA repair gene mutations in patients with prostate cancer (around 20%) and the antitumor response of PARP inhibitors make it a possible short-term therapeutic strategy with several registering clinical trials ongoing.
Bulletin du cancer. 2018 Sep 29 [Epub ahead of print]
Yohann Loriot, Guillaume Meynard, Elodie Klajer, Clément Bolognini, Noémie Gassian, Antoine Thiery-Vuillemin
Gustave-Roussy, département de médecine, Inserm U981, 114, rue Édouard-Vaillant, 94805 Villejuif, France., CHU de Besançon, oncologie, 25030 Besançon cedex, France., CHU de Besançon, oncologie, 25030 Besançon cedex, France; Inserm, UMR1098, 25020 Besançon cedex, France; Université de Franche-Comté, UMR1098, SFR IBCT, 25020 Besançon, France. Electronic address: .