DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology

Prostate cancer (PCa) has a distinct molecular signature, including characteristic chromosomal translocations, gene deletions and defective DNA damage repair mechanisms. One crucial pathway involved is homologous recombination deficiency (HRD) it found in almost 20% of metastatic castrate-resistant PCa (mCRPC). Inherited/germline mutations are associated with hereditary predisposition to early development aggressive behavior. BRCA2, ATM CHECK2 the most frequently HRD-mutated genes. BRCA2-mutated tumors have unfavorable clinical pathological characteristics, such as intraductal carcinoma. PARP inhibitors, due induction synthetic lethality, been therapeutically approved for mCRPC HRD alterations. Mutations detected tissue, while liquid biopsy utilized during follow-up, recognizing acquired resistance The mismatch (MMR) another mechanism implicated carcinogenesis, although only 5% affected. It disease. PD-1 inhibitors used MMR-deficient tumors; thus, MMR status should be tested all cases. A surrogate marker mechanisms tumor mutational burden. PDL-1 expression intratumoral lymphocytes ambivalent predictive value. Few experimental molecules so far proposed potential biomarkers. Future research may further elucidate role pathways PCa, revealing new therapeutic targets