Abstract 3680: Loss of ARID1A expression leads to sensitivity to ROS-inducing agents in ovarian cancer cells

AT-rich interactive domain-containing protein 1A (ARID1A) is frequently inactivated by mutations in a broad spectrum of cancer types, including ovarian and endometrial cancers. However, therapeutic strategies targeting ARID1A-mutant cancers remain limited. In this study, we aimed to identify drugs that selectively target ARID1A-mutant ovarian cancer cells. To this end, we compared the drug sensitivities of ARID1A-mutant and ARID1A-wildtype cancer cell lines using the Genomics of Drug Sensitivity in Cancer database. We found that ARID1A-mutant cancer cell lines were more sensitive to treatment with the reactive oxygen species (ROS)-inducing agent elesclomol compared to ARID1A-wildtype cancer cell lines. We validated this finding in a panel of ovarian and endometrial cancer cell lines, observing that treatment with elesclomol inhibited growth and induced apoptosis more potently in ARID1A-mutant cells than in ARID1A-wildtype cells. Knockdown of ARID1A expression in ARID1A-wildtype cells resulted in increased sensitivity to ROS-inducing agents, whereas re-expression of ARID1A in ARID1A-mutant cells resulted in decreased sensitivity. Finally, we found that knockdown of ARID1A expression resulted in increased intracellular ROS levels and subsequently promoted cell growth. In summary, we identified a novel role for ARID1A in protecting cells from oxidative stress and that ROS-inducing agents may be used to target ARID1A-mutant ovarian cancer cells. Citation Format: Suet-Yan Kwan, Kwong-Kwok Wong. Loss of ARID1A expression leads to sensitivity to ROS-inducing agents in ovarian cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3680.