While the role of ADAM17 and its specific substrates (e.g., EGFR ligands, Notch, sIL-6R) has been previously documented in several cancers (e.g., lung cancer, CRC, pancreatic cancer, breast cancer) [29,41,42,43,61,97,132,177,182,187,194,195,196,197], for the purpose of this review, we will focus on lung cancer, for which many mechanistic insights are relevant to other cancer types. This evidence concerns the gene ADAM17 and familial pancreatic carcinoma.