Induction of a metabolic switch from glucose to ketone metabolism programs ketogenic diet-induced therapeutic vulnerability in lung cancer

This study found that lung tumor-initiating cells (TICs), unlike bulk tumor cells, can switch from glucose to ketone use under glucose deprivation. Ex vivo ketone supplementation or a prolonged ketogenic diet supported TIC growth and tumor-initiating capacity, and ketones fueled ketolysis, fatty acid synthesis and de novo lipogenesis. Ketogenic diet intervention sensitized TICs to inhibition of the ketone transporter MCT1 and its chaperone CD147, and to blockade of fatty acid synthase. Loss of CD147 ablated TICs under glucose limitation in vitro and in vivo.