This is the case of kidney cancers, where transitory activation of the NRF2 signature protects the kidney epithelium from carcinogens and chemotherapies such as cisplatin, while its hyperactivation in ccRCC and PRCC is crucial in supporting a malignant phenotype and chemoresistance [36,37]. The gene discussed is PRCC; the disease is nonpapillary renal cell carcinoma.