Dual Blockade of EGFR and c-Met Abrogates Redundant Signaling and Proliferation in Head and Neck Carcinoma Cells

摘要: Purpose: Head and neck squamous cell carcinoma (HNSCC) is usually fatal, innovative approaches targeting growth pathways are necessary to effectively treat this disease. Both the epidermal factor receptor (EGFR) hepatocyte (HGF)/c-Met overexpressed in HNSCC initiate similar downstream signaling pathways. c-Met may act consort with EGFR and/or be activated as a compensatory pathway presence of blockade. Experimental Design: Expression levels were determined by Western analysis lines correlated antitumor responses inhibitors these Results: Combining inhibitor PF2341066 gefitinib abrogated proliferation, invasion, wound healing significantly more than inhibition each alone lines. When both HGF ligand, TGF-α, present vitro , P-AKT P-MAPK expression maximally inhibited pathways, suggesting that or can compensate when phosphorylation other inhibited. We also showed TGF-α induce over sixfold 8 hours absence HGF, supporting ligand-independent mechanism. Combined resulted an enhanced tumor volumes accompanied decreased number proliferating cells increased apoptosis compared single agent treatment vivo . Conclusions: Together, results suggest dual blockade promising clinical therapeutic strategy for treating HNSCC. Clin Cancer Res; 17(13); 4425–38. ©2011 AACR