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Preliminary expert recommendations published in 2001 were subsequently formalized into comprehensive guidelines in 2002, which continue to provide pivotal scientific direction (519, 520)

The administration of System X c inhibitors can deplete intracellular cysteine, reduce GSH concentration, trigger OS, and increase cell sensitivity to ferroptosis ( Small molecule erastin can directly and selectively target and inhibit the System X c , and irreversibly bind to and inactivate XCT, leading to continuous disorder of cystine uptake, a decrease in cellular antioxidant capacity, and eventually ROS accumulation and ferroptosis (Sato et al., 2018