Clinical significance of mutations in DNA repair genes in patients with metastatic prostate cancer

Abstract

Prostate cancer (PCa) is one of the most common malignant tumor in men. Significant advances have been made in the early detection and treatment of localized PCa, but metastatic castration-resistant PCa (mCRPC) remains one of the most challenging problems to treat in oncology. To improve treatment outcomes for patients at this stage of the disease, it is necessary to develop personalized therapy options based on the definition of biological predictors. In mCRPC, mutations in DNA repair genes are detected in ~23 % of patients with mCRPC. Detection of these mutations in patients with PCa has important clinical relevance. PCa with mutations in DNA repair genes may be sensitive to poly(ADP-ribose)-polymerase (PARP) inhibitors. Several studies II and III phase have demonstrated the effectiveness of PARP inhibitors with a high objective response rate in the treatment of mCRPC in patients with mutations in the DNA repair genes, which is definitely a more personalized approach to treatment. Identification of hereditary mutations in DNA repair genes is an important prognostic factor for the proband's relatives (for both men and women), which can later be used for genetic counseling of patients and the application of strategies to reduce the risk of malignant diseases.