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Following endosomal acidification, Fe³ + dissociates from transferrin, is reduced to Fe² + by STEAP3, and subsequently released into the labile iron pool (LIP) via DMT1 ( Notably, this Fe² + accumulation is not accidental—it is a metabolic trade-off for drug resistance: resistant cells rely on increased iron to support rapid proliferation and DNA repair under therapeutic stress, but this dependence simultaneously amplifies their vulnerability to ferroptosis

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however, whether this is due to intrinsic activity or through a binding partner remains to be verified (82)