TP53 and cancer: Since normal cells can mount an optimal NRF2-mediated response to oxidative stress (Fig. 9b), we propose that accumulation of mut-p53 in cancer cells, through its repressive effects on NRF2 activity and SLC7A11 expression, creates an ‘Achilles heel' that can be exploited by further inhibition of system xC− (Fig. 9d).