Potential agnostic role of BRCA alterations in patients with several solid tumors: One for all, all for one?

Germline BRCA1/2 alterations in the Homologous Recombination (HR) pathway are considered as main susceptibility biomarkers to Hereditary Breast and Ovarian Cancers (HBOC). The modern molecular biology technologies allowed to characterize germline and somatic BRCA1/2 alterations in several malignanci...

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Published in:Critical reviews in oncology/hematology 2023-10, Vol.190, p.104086, Article 104086
Main Authors: Fanale, Daniele, Corsini, Lidia Rita, Pedone, Erika, Randazzo, Ugo, Fiorino, Alessia, Di Piazza, Marianna, Brando, Chiara, Magrin, Luigi, Contino, Silvia, Piraino, Paola, Bazan Russo, Tancredi Didier, Cipolla, Calogero, Russo, Antonio, Bazan, Viviana
Format: Article
Language:English
Subjects:
Agnostic indication
BRCA1/2
Breast cancer
HBOC syndrome
Homologous Recombination Deficiency
Ovarian cancer
PARP inhibitors
Solid tumors
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Summary:Germline BRCA1/2 alterations in the Homologous Recombination (HR) pathway are considered as main susceptibility biomarkers to Hereditary Breast and Ovarian Cancers (HBOC). The modern molecular biology technologies allowed to characterize germline and somatic BRCA1/2 alterations in several malignancies, broadening the landscape of BRCA1/2-alterated tumors. In the last years, BRCA genetic testing, beyond the preventive value, also assumed a predictive and prognostic significance for patient management. The approval of molecules with agnostic indication is leading to a new clinical model, defined "mutational". Among these drugs, the Poly (ADP)-Ribose Polymerase inhibitors (PARPi) for BRCA1/2-deficient tumors were widely studied leading to increasing therapeutic implications. In this Review we provided an overview of the main clinical studies describing the association between BRCA-mutated tumors and PARPi response, focusing on the controversial evidence about the potential agnostic indication based on BRCA1/2 alterations in several solid tumors. [Display omitted] •BRCA mutational status showed important therapeutic implications in HBOC patients.•BRCA alterations may be potential predictive biomarkers of PARPi response in cancer.•The tumor-agnostic BRCA1/2 evaluation could have a significant clinical impact.
ISSN:1040-8428
1879-0461
1879-0461
DOI:10.1016/j.critrevonc.2023.104086