Development of RAD51 degraders for ovarian cancer treatment
PARP inhibitor drugs have had a major impact on the clinical treatment of ovarian cancer in recent years, but they do not work in all patients. Many tumors have genetic mutations that make the tumor unable to repair damage to its DNA. PARP inhibitors exploit this fact and are an effective treatment for these tumors. However, not all tumors have mutations in the DNA repair genes, so PARP inhibitors do not work on them. Dr. Chien therefore aims to develop drugs that disrupt DNA repair in tumors in order to make PARP inhibitors effective in all ovarian cancer patients. He will combine two emerging technologies, a drug designing method and a drug discovery platform, to make a drug that can degrade a protein called RAD51. RAD51 is critical for DNA repair, so destroying it specifically in ovarian cancer cells will make the tumor responsive to PARP inhibitors. This study will demonstrate the power of this novel drug designing method and open the door to developing more drugs to improve treatment. Successful drugs will have significant clinical impact by making PARP inhibitors an effective treatment for all ovarian cancer patients, even those whose tumors have developed resistance to PARP inhibitors.