Abstract 2892: EGLN1 is a synthetic lethal target in ARID1A-mutant ovarian cancer

The successful use of PARP inhibitors for the treatment of BRCA-mutant ovarian cancer underscores the importance of synthetic lethality as a therapeutic opportunity for tumors with loss-of-function mutations in tumor suppressor genes. Ovarian cancer ranks as the fifth deadliest cancer among women, and one ovarian cancer subtype, clear cell carcinoma, is particularly underserved. The most frequent genetic alteration in ovarian clear-cell carcinoma is loss-of-function mutation of the SWI/SNF-A complex subunit, ARID1A. We interrogated the data published by Project Achilles to determine candidate synthetic lethal partners with ARID1A in ovarian cancer, and identified EGLN1, a member of the EglN-family of prolyl hydroxylases. Inhibition of EGLN1, either genetically or pharmacologically, leads to decreased viability in ovarian cancer cell lines. Pharmacological inhibition of EGLN1 is clinically achievable as evidenced by several well-tolerated, small molecule inhibitors currently in clinical trials for the treatment of anemia in the context of chronic kidney disease. The synthetic lethal interaction of ARID1A and EGLN1 may provide a therapeutic opportunity for patients diagnosed with ovarian clear-cell carcinoma. Citation Format: Kimberly J. Briggs, Chengyin Min, Hongxiang Zhang, Alan Huang. EGLN1 is a synthetic lethal target in ARID1A -mutant ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2892.