학술논문
Homologous Recombination Repair Deficiency in Metastatic Prostate Cancer: New Therapeutic Opportunities.
Document Type
Article
Author
Piombino, Claudia; Pipitone, Stefania; Tonni, Elena; Mastrodomenico, Luciana; Oltrecolli, Marco; Tchawa, Cyrielle; Matranga, Rossana; Roccabruna, Sara; D'Agostino, Elisa; Pirola, Marta; Bacchelli, Francesca; Baldessari, Cinzia; Baschieri, Maria Cristina; Dominici, Massimo; Sabbatini, Roberto; Vitale, Maria Giuseppa
Source
Subject
*HOMOLOGOUS recombination
*DNA repair
*PROSTATE cancer
*METASTASIS
*ANDROGEN receptors
*CLINICAL trials
*LUTEINIZING hormone releasing hormone
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Language
ISSN
1661-6596
Abstract
More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript. [ABSTRACT FROM AUTHOR]