Inhibiting the system xC−/glutathione axis selectively targets cancers with mutant-p53 accumulation

TP53, a critical tumour suppressor gene, is mutated in over half of all cancers resulting in mutant-p53 protein accumulation and poor patient survival. Therapeutic strategies to target mutant-p53 cancers are urgently needed. We show that accumulated mutant-p53 protein suppresses the expression of SLC7A11, a component of the cystine/glutamate antiporter, system xC-, through binding to the master antioxidant transcription factor NRF2. This...