doi: 10.1056/NEJMe2202547 123 IottiS.WolfF.MazurA.MaierJ
Central to this is the ability of the copper ion to transition between the oxidation states Cu(II) and Cu(I)
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For the most of the commonly used drugs, the hypoxic TME rich in HIF-1 plays a major role in the development of drug resistance through multiple pathways [3,18-32]
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This process, along with GCL inhibition and the formation of mixed disulfides between GSH and protein sulfhydryl, concurred to a steady-state decrement of free GSH concentration and, consequently, to an intracellular redox state shift toward more oxidizing conditions, which could be required for avoiding fast reduction of oxidized cysteines allowing the upstream ROS-induced autophagic stimulus to be propagated