ICE Bioscience Posters

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KRAS mutations are dominant oncogenic drivers in many solid tumors. Although KRAS G12C inhibitors and pan-RAS targeted agents have shown clinical promise, intrinsic and acquired resistance remains a major challenge. Here, we established a well-validated panel of resistant cell lines against KRAS G12C/G12D inhibitors, pan-RAS molecular glues, and pan-RAS inhibitors. We performed multi-omics characterization, cross-resistance profiling, and genomic analysis to define key resistance features, including copy number alterations and secondary KRAS mutations. We further evaluated diverse combination strategies to overcome RAS-driven resistance in this platform. This model provides a robust preclinical system for investigating resistance mechanisms and supporting next-generation RAS-targeted therapy development.