Abstract 3484: Mechanism of BRAF V600E resistance revealed by cell panel screening and bioinformatics

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Abstract The BRAF V600E mutation is pivotal target in the treatment of melanoma. Dabrafenib, one of the most potent inhibitors approved by the FDA, exhibits differential sensitivity across different cancer types. To explore the underlying mechanisms responsible for the resistance of certain cancers to Dabrafenib, we tested a panel of 20 BRAF V600E positive cancer cell lines. Our results showed that 15 of these cell lines demonstrated sensitivity to Dabrafenib, whereas the remaining 5 exhibited resistance. We then investigated the correlation between Dabrafenib potency and gene expression patterns based on public high throughput sequencing data via bioinformatics methods. The results uncovered that the cell lines resistant to Dabrafenib showed low expression of MAP3K1, alongside with elevated expression of G0S2 and PIK3CG. These alterations are known to promote tumor cell proliferation, migration, and invasion, thereby contributing to a reduced sensitivity to BRAF inhibitors. Subsequent in vitro experiments validated the findings derived from our analysis. This unbiased, bioinformatics-driven approach provides valuable insight into the reasons behind treatment resistance and aids in the development of next-generation treatment approaches for inhibitor-resistant cancers. Citation Format: Kaiqiang Hu, Qiuyuan Yang, Pengwei Pan, Fang He. Mechanism of BRAF V600E resistance revealed by cell panel screening and bioinformatics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3484.

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