Abstract 4929: ICX-101, a novel MYC inhibitor, shows antitumor activity in patient-derived cells of advanced lung cancer with high MYC expression

Abstract

Abstract Background: MYC is an attractive therapeutic target in lung cancer. ICX-101 is a novel potent, selective small molecule that directly inhibits the binding of MYC/MAX dimers to the DNA binding sequence E-box. Here, we show that ICX-101 shows antitumor activity in patient-derived cells (PDC) of advanced lung cancer and that the drug responses are correlated with the MYC expression levels. Methods: PDCs of lung cancer were treated with ICX-101, and the area under the dose-response curve (AUC) was measured as the readout for antitumor efficacy. MYC expression level of each PDC was measured with the fold expression of mRNA compared to the normal lung tissue. The patient’s clinical data and survival outcomes were analyzed to correlate with the drug responses of PDCs. Results: We collected 100 PDCs from 82 lung cancer patients. The histologic types included adenocarcinoma (N = 82), squamous cell carcinoma (N = 10), non-small cell lung cancer (NSCLC) not otherwise specified (NOS) (N = 4), and small cell lung cancer (SCLC, N = 4). PDCs derived from SCLC showed higher MYC expression levels than NSCLC (P = 0.004). MYC was a prognostic factor, as the patient groups with the top and bottom 25 percentiles of MYC mRNA expression had an overall survival of 932.5 and 256 days, respectively (P = 0.029). However, MYC expression was predictive for the response to ICX-101, as the PDCs with the top 25 percentiles of MYC levels showed markedly lower AUC values than those with the bottom 25 percentile (P < 0.001). Additionally, the MYC mRNA levels and AUC values were inversely correlated with statistical significance (R = -0.46, P < 0.001). Conclusion: ICX-101 is a potent MYC inhibitor that shows antitumor activity in lung cancer PDCs. Our results suggest the potential of ICX-101 as a possible therapeutic option in advanced lung cancer with high MYC expressions. Citation Format: Wonyoung Choi, Kyung-Chae Jeong, Seog-Yun Park, Sunshin Kim, Eun Hye Kang, Mihwa Hwang, Ji-Youn Han. ICX-101, a novel MYC inhibitor, shows antitumor activity in patient-derived cells of advanced lung cancer with high MYC expression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4929.