DNA Mismatch Repair in Advanced Metastatic Prostate Carcinoma: Clinical Perspective

Abstract

Prostate carcinoma (PCa) is among the most frequently diagnosed cancer in men worldwide. Men with metastatic PCa receive primary androgen deprivation therapy (ADT). However, nearly all men will develop resistance to primary ADT, a state known as castration-resistant prostate carcinoma a (CRPC). Several therapeutic drugs with different mechanisms of action have been approved for CRPC including systemic chemotherapeutics (docetaxel and cabazitaxel) and drugs targeting the resistance pathways leading to CRPC, including enzalutamide and abiraterone. Despite significant survival benefit, resistance to these therapies develops rapidly. Thus, deciphering the mechanisms of resistance and pathways leading to progression is the most critical objectives in PCa research. Some proofof-concept clinical trials have identified that personalized therapies with PARP inhibition, platinum chemotherapy, and immunotherapy may be beneficial to a subset of PCa and CRCP with underlying DNA repair defects. This review aims to address the potential therapeutic implication of Mismatch repair (MMR) pathways in advanced PCa and CRPC.