Abstract
Simple SummaryHistorically, the treatment of prostate cancer was a blanket approach for all. Prostate cancer has not benefitted from targeted treatments based on specific tumour characteristics (ie. Particular genetic or molecular patterns) the way other cancers have. This is important as studies have shown that prostate cancer patients with certain errors in their genes, such as BRCA2 or BRCA1, are more likely to have worse disease and poorer outcome. These patients can be treated successfully with a group of drugs called ‘PARP inhibitors’. This paper examines the prognostic, clinical and therapeutic role of BRCA2/BRCA1 mutations across the evolution of PCa. The impact of the inclusion of BRCA genes on genetic screening will also be outlined.Studies have demonstrated that men with Prostate Cancer (PCa) harboring BRCA2/BRCA1 genetic aberrations, are more likely to have worse disease and a poorer prognosis. A mutation in BRCA2 is known to confer the highest risk of PCa for men (8.6 fold in men ≤65 years) making BRCA genes a conceivable genomic biomarker for risk in PCa. These genes have attracted a lot of research attention however their role in the clinical assessment and treatment of PCa remains complex. Multiple studies have been published examining the relationship between prostate cancer and BRCA mutations. Here BRCA mutations are explored specifically as a biomarker for risk in PCa. It is in this context, we examined the prognostic, clinical and therapeutic role of BRCA2/BRCA1 mutations across the evolution of PCa. The impact of the inclusion of BRCA genes on genetic screening will also be outlined.
Highlights
Prostate Cancer (PCa) was the second most common cancer diagnosis made in men (14.1%) and the fifth leading cause of death (6.8%) worldwide in 2020 [1]
The median OS of all BRCA2 mutation carriers was reported by Edwards et al as significantly shorter at 4.8 years compared with that of non-carriers at 8.5 years (p = 0.003) and that poorer survival was associated with the presence of a germline BRCA2 mutation, which was independent from stage or histology at time of diagnosis [40]
Platinum chemotherapy generates interstrand cross-links that can only be adequately repaired by homologous recombination (HR) based DNA repair, and BRCA1 and BRCA2 mutated cells are highly sensitive to platinum chemotherapy both in vitro and in vivo [79]
Summary
Prostate Cancer (PCa) was the second most common cancer diagnosis made in men (14.1%) and the fifth leading cause of death (6.8%) worldwide in 2020 [1]. When functioning correctly BRCA1/BRCA2 are important tumor suppressor genes with multiple functions including transcription and complex cell cycle control [8] Their primary role is in the repair of DNA double stranded breaks (DSB) through the initiation of homologous recombination (HR). A mutation in BRCA2 is known to confer the highest risk of PCa for men (8.6 fold in men ≤65 years), with BRCA1 demonstrating increased risk, albeit to a lesser extent (3.5 fold) [10]. These genes have attracted a lot of research attention their role in the clinical assessment and treatment of PCa remains complex.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
