INCB3619, a specific ADAM17 metalloproteinase inhibitor, blocked HER3 signaling in gefitinib-resistant NSCLC cell lines.[165] D1(A12), another ADAM17 inhibitor, decreased pro-tumor signaling in HNSCC and ovarian cancer models.[48, 166] Batimastat (BB-94), a broad spectrum anti-metalloproteinase, prevented HER3 phosphorylation and Erk activation in fulvestrant-resistant breast cancer cell lines in a mechanism independent of ADAM17, suggesting potential therapeutic application in breast cancer.[167] Early clinical trials to evaluate safety and efficacy of these agents are expected. This evidence concerns the gene ADAM17 and head and neck squamous cell carcinoma.