Abstract 7217: Synergistic anti-cancer effects of dual IGF-1R and EGFR targeting in uveal melanoma

Abstract Uveal melanoma arises from melanocytes in the eye, with approximately 7, 000 patients reported worldwide every year. IGF-1R plays an important role in uveal melanoma metastatic progression, and promotes tumor cell proliferation and survival. However, in previously reported clinical trials, targeting IGF-1R did not significantly inhibit uveal melanoma metastatic spread or patient survival. This could be due to compensatory activation of other receptor signaling pathways. Therefore, the aim of this study is to find other activated receptors in uveal melanoma cells following IGF-1R inhibition which could be co-targeted in a novel combination treatment for metastatic uveal melanoma. Using several uveal melanoma cell lines (Mel202, Omm2.3, Omm2.5, Omm1, 92.1, MP38 and MM28), we found that treatment with linsitinib, an IGF-1R inhibitor, increased EGFR protein expression and activity. Targeting IGF-1R alone with linsitinib, or EGFR alone with gefitinib, did not significantly inhibit growth of uveal melanoma cells. However, combination treatment with linsitinib (10µM) and gefitinib (5µM) significantly inhibited both cell growth and anchorage-dependent/independent colony formation abilities in uveal melanoma cultures. Moreover, Linsitinib and gefitinib co-treatment dramatically increased cleaved PARP protein, an apoptotic maker. Our research suggests that dual targeting of IGF-1R and EGFR could be a novel treatment strategy to inhibit uveal melanoma metastatic dissemination and growth. Citation Format: Pei-Chi Tsai, Charles G. Eberhart, Su-Chan Lee. Synergistic anti-cancer effects of dual IGF-1R and EGFR targeting in uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7217.