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A reduction in the glutathione precursors, glutamine and glycine, further reveals dysregulation of this pathway in tumors under high glucose abundance ( Extended Data Fig

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287 Increasing preclinical and clinical evidence suggests that TGF- signaling activation in established anti-cancer therapies such as targeted therapies, chemotherapy, and radiation is a driver of drug resistance, 288,289 involving multiple mechanisms such as induction of EMT, metabolic reprogramming, activation of alternative pathways, promotion of an immune-suppressive microenvironment, induction of a stem cell-like phenotype, and promotion of drug uptake and efflux