Increased purinergic signaling regulated by PI3K pathway-dependent activation of E2F transcription factor 1 (E2F1) mediated by the cyclin D-cyclin-dependent kinase 4/6 complex facilitates HCC tumorigenesis, indicating the possibility of targeting purine metabolic reprogramming as a potential treatment for patients with HCC [93]. This evidence concerns the gene CDK4 and hepatocellular carcinoma.