Hua E Yu, PhD
Beckman Research Institute of the City of Hope
2020 Karla Mooers Pilot Study Award
Targeting dePARylation activates anti-ovarian cancer immune responses
The FDA has approved several types of PARP inhibitors for treating ovarian cancer. These drugs are especially effective at killing tumor cells that cannot repair damage that occurs to their DNA. One of the challenges with PARP inhibitors is that they can suppress the anti-tumor response of the patient’s own immune system. Dr. Yu is proposing to test another class of drugs, called PARG inhibitors, which target a similar cellular process as PARP inhibitors. Dr. Yu has developed a potent PARG inhibitor that preferentially kills cancer cells with defects in repairing damaged DNA, similar to PARP inhibitors. Unlike PARP inhibitors, however, PARG inhibitors actually activate the patient’s immune response, suggesting that PARG inhibitors may have superior anti-tumor effects than PARP inhibitors. The mechanisms by which PARG inhibitors activate anti-tumor immune responses are not understood. In this study, Dr. Hu will compare the immune response and anti-tumor effects of PARP and PARG inhibiting drugs by using both a mouse model of ovarian cancer and immune cells from patients. By providing proof-of-concept that PARG inhibitors are potent anti-ovarian cancer drugs, these studies may lead to novel therapies to improve the treatment outcomes of ovarian cancer patients.