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The ssGSEA R package was used to calculate four metabolic mode scores of each patient in indicated datasets based on corresponding metabolic gene-sets (Glycolysis, oxidative phosphorylation, fatty acid, and glutamine metabolism) downloaded from Gene Set Enrichment Analysis website (GSEA, (Supplementary Data 1)

Bypass pathway activation engages alternative drivers, including MET, AXL or HER2 amplification, as well as RAS/MAPK or PI3K mutations

Cyclosporin A is a broad-spectrum multidrug resistance modulator

HK2-driven glycolysis, autophagy, and immunosuppression are critical in mediating drug resistance in cancer [134,135,136]