2020/10/27 by Rebeca Lozano, Elena Castro, Isabel M. Aragón +5 · 110 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Bioinformatics #Biology #Cancer #Cancer research #DNA Repair Mechanisms #DNA repair #Disease #Gene #Genetics #Germline #Germline mutation #Internal medicine #Medicine #Mutation #Oncology #PARP inhibition in cancer therapy #Pathology #Precision medicine #Prostate #Prostate Cancer Treatment and Research #Prostate cancer
paper · doi:10.1038/s41416-020-01114-x
published in British Journal of Cancer 124(3), 552-563 (Springer Nature)
openalex publication_date 2020/10/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Over the past years, several studies have demonstrated that defects in DNA damage response and repair (DDR) genes are present in a significant proportion of patients with prostate cancer. These alterations, particularly mutations in BRCA2, are known to be associated with an increased risk of developing prostate cancer and more aggressive forms of the disease. There is growing evidence that certain DDR gene aberrations confer sensitivity to poly-(ADP ribose) polymerase inhibitors and/or platinum chemotherapy, while other defects might identify cases that are more likely to benefit from immune checkpoint inhibition. The potential prognostic impact and relevance for treatment selection together with the decreasing costs and broader accessibility to next-generation sequencing have already resulted in the increased frequency of genetic profiling of prostate tumours. Remarkably, almost half of all DDR genetic defects can occur in the germline, and prostate cancer patients identified as mutation carriers, as well as their families, will require appropriate genetic counselling. In this review, we summarise the current knowledge regarding the biology and clinical implications of DDR defects in prostate cancer, and outline how this evidence is prompting a change in the treatment landscape of the disease.