Targeting STAT3 Signaling for Immune Checkpoint Blockade to Augment PARP Inhibitor Therapy in BRCA-Mutated Ovarian Cancer
PARP inhibitors and immune checkpoint inhibitors are two promising new therapies for ovarian cancer patients who have mutations in the BRCA gene. BRCA-mutated ovarian cancer cells produce a protein called PD-L1 to avoid being recognized and killed by immune cells. The anti-PD-L1 immune checkpoint inhibitor is used therapeutically to mask PD-L1, thereby enabling the body’s immune cells to attack BRCA-mutated ovarian cancer. Meanwhile, PARP inhibitor drugs prevent BRCA-mutated ovarian cancer cells from repairing DNA, causing these cancer cells to die. Using a PARP inhibitor in combination with an immune checkpoint inhibitor is much more effective at killing BRCA-mutated ovarian cancer than either of these inhibitors alone.
Unfortunately, the anti-PD-L1 immune checkpoint inhibitor works for few patients and loses its effectiveness over time. To address this issue, Dr. Lin will investigate how to stop ovarian cancer from producing PD-L1 in the first place by using a drug that inhibits the STAT3 protein. This therapeutic approach will make immune cells more capable of mounting attacks on ovarian cancer. Ultimately, this Bridge Funding Award project could provide the rationale for using a STAT3 inhibitor together with a PARP inhibitor as a highly effective combination therapy to treat this devastating disease.