PDK1 and cancer: Mechanistically, the NRF2 activation can promote the metabolic reprogramming of cancer cells by enhancing the transcription of genes encoding glycolytic enzymes while inhibiting the conversion of pyruvate to acetyl-CoA by directly activating pyruvate dehydrogenase kinase 1 (PDK1), leading to the inhibition of the tricarboxylic acid (TCA) cycle in the cancer-initiating cells.