San Antonio, Texas USA (UroToday.com) Human cells have several methods for DNA repair such as single strand repair of base pair mismatch repair. These methods are heavily involved in the malignant process and provide potential targets for treatment of cancer in general and prostate cancer specifically.
Treatment focused on DNA repair pathway is not new. Radiation therapy is based on the notion of creating enormous DNA damage thus over whelming the DNA repair mechanisms and thus inducing apoptosis in the cell. Etoposide chemotherapy works in a similar manner. It is well known that at least 20% of mCRPC patients have deficient DNA repair mechanisms. Furthermore, 10% of these patients harbor a germline mutation in DNA repair genes. The most common gene is BRCA2 but BRCA1 and ATM are well established as well. A novel intervention target in mCRPC patient is the PARP protein. PARP protein plays a significant role in single strand repair. Olaparib is a new PARP inhibitor that has been approved for treatment of metastatic ovarian cancer. This molecule was also examined in mCRPC patients. Out of 50 patients with established mCRPC, 20 had at least a partial response to Olaparib. It was shown that the patients that responded to the PARP inhibitor expressed germline mutations in DNA repair genes (e.g. BRCA2). In conclusion, there is a strong biological and early clinical rationale for the investigation of DNA repair pathways targeting agents in subsets of patients with prostate cancer. An estimate of 15-30% of patients may benefit from these agents. The investigation of the role of some DNA repair associated genes is ongoing. Lastly, investigating more aggressive approaches early in the disease may be appropriate for men who harbor mutations in DNA repair genes.
Presented By: Wassim Abida
Written By: Miki Haifler, MD, M.Sc., Society of Urologic Oncology Fellow, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA