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Abbreviations HGF: hepatocyte growth factor ICIs: immune checkpoint inhibitors TME: tumor microenvironment EMT: epithelial-mesenchymal transition HNSCC: head and neck squamous cell carcinoma RTKs: receptor tyrosine kinases METex14: MET exon 14 skipping mutations NSCLC: non-small cell lung cancer CAFs: cancer-associated fibroblasts TAMs: tumor-associated macrophages MDSCs: myeloid-derived suppressor cells NK: natural killer DCs: dendritic cells ECM: extracellular matrix Chi3L1: chitinase-3-like-1 Treg: T regulatory CRC: colorectal cancer GC: gastric cancer IL-6R: interleukin-6 receptor MMPs: matrix metalloproteinases HIF1: hypoxia-inducible factor 1 IFN-: interferon-gamma HCC: hepatocellular carcinoma CTLs: cytotoxic T lymphocytes MSCs: Mesenchymal stromal cells CTLA-4: cytotoxic T-lymphocyte-associated protein 4 APCs: antigen-presenting cells ORR: objective response rate PFS: progression-free survival OS: overall survival GSK3: glycogen synthase kinase 3 References Knowles LM, Stabile LP, Egloff AM, Rothstein ME, Thomas SM, Gubish CT, Lerner EC, Seethala RR, Suzuki S, Quesnelle KM, et al

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This pattern suggests continuous daily Dihexa administration beyond 4-6 weeks without rest periods would likely trigger protective receptor downregulation, reducing compound effectiveness over time

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