ADAM17 and hepatocellular carcinoma: The hypoxic microenvironment is a prominent and common feature in many solid tumors, including PC,452 HCC,453 breast cancer,454 and melanoma.455 Hypoxia plays a role in mediating the malignant biological behavior of cancer cells and can impact the therapeutic outcomes of tumors through complex mechanisms.456,457 In glioma cells, Grassi et al.458 revealed that hypoxia induces the release of intracellular fragments of DLL1, a Notch ligand, which is dependent on ADAM17 and HIF1α/HIF2α.