Metastatic castration-resistant prostate cancer with HRR gene mutation

Metastatic castration-resistant prostate cancer with homologous recombination repair (HRR) gene mutation is an advanced malignancy of the male genitourinary system that has disseminated beyond the prostate to distant sites, such as bone, lymph nodes, or visceral organs The condition is clinically defined by disease progression—evidenced by rising prostate-specific antigen levels or worsening radiographic lesions—despite medical or surgical androgen deprivation therapy achieving castrate levels o...

Metastatic castration-resistant prostate cancer with homologous recombination repair (HRR) gene mutation is an advanced malignancy of the male genitourinary system that has disseminated beyond the prostate to distant sites, such as bone, lymph nodes, or visceral organs

Pathophysiologically, these tumors harbor deleterious germline or somatic mutations in genes responsible for error-free double-strand DNA repair via homologous recombination (commonly including BRCA1, BRCA2, and ATM) This underlying genomic instability confers an aggressive disease biology while rendering the tumor selectively vulnerable to targeted DNA-damaging mechanisms, such as poly(ADP-ribose) polymerase (PARP) inhibition

This underlying genomic instability confers an aggressive disease biology while rendering the tumor selectively vulnerable to targeted DNA-damaging mechanisms, such as poly(ADP-ribose) polymerase (PARP) inhibition