Christopher J. Kemp, PhD
Fred Hutchinson Cancer Research Center
2019 Sequoyah Electric Pilot Study Award
Preclinical advancement of combination therapy targeting BAZ2A and EZH2 in ovarian clear cell carcinoma
Ovarian cancer accounts for over 14,000 deaths in the United States every year. Although ovarian cancer has several subtypes, patients have been treated almost in the same way. Precision medicine is a treatment approach in which drugs target abnormal genomic changes unique to each cancer. Dr. Kemp is focusing on clear cell carcinoma of the ovary (OCCC), a rare but chemotherapy-resistant subtype. Up to 60% of OCCC have mutations in the ARID1A gene. Recent studies have shown that ARID1A-mutated OCCC can be targeted with inhibitors of the EZH2 protein. Dr. Kemp has shown that growth of ARID1A-mutated OCCC can also be blocked by inhibiting the BAZ2A protein. Importantly, when inhibitors for EZH2 and BAZ2A are combined, they kill ARID1A-mutated OCCC cells even more effectively than either drug alone. In this study, Dr. Kemp and colleagues will test the effectiveness and tolerability of GSK2801, a BAZ2A inhibitor, as a combination therapy with EZH2 inhibitors using a mouse model of OCCC. They will also investigate how BAZ2A interacts with EZH2 to kill cancer cells in OCCC cells from patients. This study is the first demonstration that BAZ2A is a candidate therapeutic target for OCCC. The completed result will provide key evidence to move this drug combination forward to a clinical trial.