KRASG12C Inhibition Remodels the Non-Small Cell Lung Cancer Surfaceome to Uncover Targetable Vulnerabilities

KRAS G12C inhibitors remodel the cell surface proteome of KRAS G12C-mutant lung adenocarcinoma, and folate receptor alpha (FOLR1) emerges as a therapeutically actionable target that is significantly upregulated during treatment, part of an acute cellular state transition toward epithelial identity. Quantitative temporal proteomic profiling across cell lines, tumor models, and treatment durations identified this adaptation. Combining KRASi with mirvetuximab soravtansine-gynx, a clinically approved FOLR1-targeting antibody drug conjugate, enhanced tumor cell cytotoxicity and deepened response and tumor control in cellular and in vivo models.