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KRAS mutation and high glucose promote O-GlcNAcylation of CLDN18.2 in pancreatic cancer, pushing the protein off the cell membrane, boosting metastasis, and weakening CLDN18.2-targeted therapy. Low-dose MRTX1133 may restore sensitivity.
Combining MEK inhibitor trametinib with pan-RTK inhibitor anlotinib shows high efficacy and manageable toxicity in treating advanced non-G12C KRAS-mutant NSCLC, overcoming adaptive resistance and offering improved clinical outcomes.
This phase II study demonstrates that the combination of avutometinib and defactinib offers significant clinical benefit with manageable safety in recurrent low-grade serous ovarian cancer, particularly in KRAS-mutant tumors.