Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer.

Castration-resistant prostate cancer is an incurable disease. To date, six agents-abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T- have shown clinical efficacy in phase III clinical trials, leading to their FDA approval. Patients are typically sequenced through most or all of these agents, and then eventually succumb to their disease. Development of new treatments remains an unmet need. We report a case of a patient who progressed on enzalutamide with a single enlarging metastatic lesion, was treated with ablative stereotactic body radiation therapy while maintaining the same systemic treatment, who then had durable complete remission. Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.

Overview for the histone codes for DNA repair.

DNA damage occurs continuously as a result of various factors-intracellular metabolism, replication, and exposure to genotoxic agents, such as ionizing radiation and chemotherapy. If left unrepaired, this damage could result in changes or mutations within the cell genomic material. There are a number of different pathways that the cell can utilize to repair these DNA breaks. However, it is of utmost interest to know how the DNA damage is signaled to the various DNA pathways. As DNA damage occurs within the chromatin, we postulate that modifications of histones are important for signaling the position of DNA damage, recruiting the DNA repair proteins to the site of damage, and creating an open structure such that the repair proteins can access the site of damage. We discuss the modifications that occur on the histones and the manner in which they relate to the type of damage that has occurred as well as the DNA repair pathways that are activated.