Abstract 2499: In vitro and in vivo efficacy of MCL1 inhibitor S63845 in small cell lung cancer

MCL1 is a member of the BCL-2 family, which regulates apoptosis. Targeting MCL1 represents a potential breakthrough of cancer treatment. We tested S63845, a MCL1 inhibitor, in four SCLC cell lines (DMS114, DMS53, SW1271, and NCI-H69) and, in addition, one patient derived SCLC cell line (KTOR201). S63845 had greater efficacy in two of five SCLC cell lines (DMS114 and KTOR201). These two SCLC cell lines had higher expression of MCL1 and lower expression of BCL-XL, which is another member of the BCL-2 family. The other three SCLC cell lines (DMS53, SW1271 and NCI-H69) were resistant to S63845 and had a higher expression of BCL-XL or lower expression of MCL1. In vivo activity was evaluated in xenograft models. DMS114 was subcutaneously implanted into immunocompromised mice. When the tumor volume was reached 150-200 mm3, mice were administered with S63845 (25 mg/kg) or vehicle intravenously twice a week. S63845 showed significant antitumor efficacy in vivo. Finally, immunohistochemical evaluation of MCL1 and BCL-XL was assessed in SCLC obtained from 33 patients at Kyoto University Hospital. High MCL1 expression with low BCL-XL expression was observed in 16 specimens (48.5%).These data suggested that S63845 might be a powerful treatment of SCLC as a new therapeutic strategy. It is possible that the expressions of MCL1 and other members of the BCL-2 family predict the sensitivity of S63845. Citation Format: Yuto Yasuda, Hiroaki Ozasa, Takahiro Tsuji, Takashi Nomizo, Tomoko Yamamoto, Hitomi Ajimizu, Hironori Yoshida, Yuichi Sakamori, Toyohiro Hirai, Young Hak Kim. In vitro and in vivo efficacy of MCL1 inhibitor S63845 in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2499.