Mechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance.

摘要: EGFR is frequently overexpressed in head and neck squamous cell cancer (HNSCC). Cetuximab a monoclonal antibody designed to interact with EGFR, block its activation, reduce the downstream signaling pathways induce internalization. This study aims investigate role of pathway internalization cetuximab-resistant line propose new therapeutic strategy optimize treatment HNSCC. The HNSCC line, CAL33 was sensitive gefitinib but resistant cetuximab. induces an unexpected phosphorylation cells similarly EGF this activation does not trigger internalization/degradation, process currently implicated response inhibits ERK AKT cetuximab-sensitive A431 cells, whereas level unmodified cells. Interestingly, harbor PIK3CA mutation. PI3K inhibitor cetuximab restores inhibition growth inhibition. Our results indicate that impaired by central element resistance. combination could be good option PIK3CA-mutated