title: Investigating BRCA Mutations: A Breakthrough in Precision Medicine of Castration-Resistant Prostate Cancer.
abstract: Despite the development of novel effective therapeutic strategies, metastatic castration-resistant prostate cancer (mCRPC) remains a disease with a lethal course and a high biological and molecular heterogeneity. To date, germline mutations in the BRCA gene represent one of the main risk factors for developing prostate cancer, with a strong association with aggressive phenotype and poor clinical outcomes. A better understanding of the genomic landscape of prostate cancer has strengthened the idea that "synthetic lethality" of this disease might be useful in cancer-drug discovery, focusing on agents such as platinum compounds and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi). In this review, we summarize the main data available on BRCA mutations and discuss the clinical implications of these genomic aberrations in the management of prostate cancer, stressing the need to identify prognostic and predictive biomarkers and to deeply understand the mechanisms of treatment resistance, in order to maximize personalized medicine protocols and therefore clinical benefit.
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modena
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. roberto.iacovelli@alice.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Department of Pathology and Diagnostics, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Department of Pathology and Diagnostics, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Fantinel
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bimbatti
authors.affiliation: Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Department of Pathology, Casa di Cura Pederzoli, Verona, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
mesh_terms: D019398:Genes, BRCA1 / Q000502:physiology*; D006801:Humans; D008297:Male; D009154:Mutation; D057285:Precision Medicine / Q000379:methods*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy