Cancer cells depend on a variety of metabolic mechanisms to defend oxidative stress, including upregulated glutathione biosynthesis, increased NADPH regeneration and suppression of ferroptosis. Solid arrows depict metabolite movement or metabolic reactions. Dashed arrows depict regulatory effects of signal transduction components. ATF4, activating transcription factor 4; NRF2, nuclear factor erythroid 2-related factor 2, also known as NFE2L2; Xc-, system Xc-, cystine/glutamate antiporter; GPX, glutathione peroxidase.