The folate cycle is a new metabolic weakness of cancer.

Cancer cells harness nutrients to support its rapid proliferation through metabolic reprogramming. Our report identified folate cycle as a metabolic target in hepatocellular carcinoma. Folate cycle stagnation via inhibition of its mitochondrial folate enzyme methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) greatly induced oxidative stress improving HCC cells' response to sorafenib.