Blocking Progression of Metastatic Prostate Cancers Prostate cancer is the most commonly diagnosed cancer among men living in the United States. In 2023 alone, more than 288,000 men are expected to be diagnosed with the disease (28). Research has shown that up to 30 percent of prostate cancers have mutations in genes that influence the homologous recombination repair (HRR) pathway (e.g., BRCA, ATM), a cellular process in which a group of proteins work together to repair DNA damage (415). Changes in the HRR pathway may result in the inability to repair DNA and lead to accumulation of mutations and cancer. Poly-ADP ribose polymerase (PARP) proteins are central to a second type of DNA repair pathway called base excision repair. Researchers have found that breast, ovarian, pancreatic, and prostate cancers with genetic mutations that lead to HRR deficiency are responsive to PARP-targeted therapeutics because disruption of these two DNA repair pathways leads to pervasive DNA damage that kills cancer cells. In July 2023, FDA approved a PARP-targeted therapeutic, talazoparib (Talzenna) for treating certain groups of men with metastatic prostate cancer carrying mutations in genes that influence the homologous recombination DNA repair pathway. Men, such as Colbert English, p. 96, who are diagnosed with metastatic prostate cancer are often treated initially with therapeutics that target androgens, the hormones that fuel prostate cancer growth. When the cancer stops responding to these treatments, it is referred to as castration-resistant prostate cancer. Talazoparib was approved in combination with the androgen-targeted therapeutic enzalutamide (Xtandi) for patients with HRR gene-mutated metastatic castrationresistant prostate cancer. Mutations in HRR genes such as BRCA1, BRCA2, and ATM were assessed prospectively using tumor tissue and/or blood-based DNA sequencing assays. The approval was based on results from a phase III clinical trial that showed that treatment with talazoparib significantly improved progression-free survival compared with treatment with enzalutamide alone (416). AACR Cancer Progress Report 2023 Advancing the Frontiers of Cancer Science and Medicine 98
RkJQdWJsaXNoZXIy NTkzMzk=