Lung cancer kills approximately 1.3 million citizens in the world annually. The tyrosine
kinase inhibitors (TKI) erlotinib and gefitinib are effective anti-tumor agents especially in lung cancer
patients with epidermal growth factor receptor (EGFR) mutations. The goal is to increase the potency
of TKI in lung cancer patients with wild type EGFR. G protein-coupled receptors (GPCR) transactivate
the wild type EGFR in lung cancer cells. The GPCR can be activated by peptide agonists causing
phosphatidylinositol turnover or stimulation of adenylylcyclase. Recently, nonpeptide antagonists were
found to inhibit the EGFR transactivation caused by peptides. Nonpeptide antagonists for bombesin (BB), neurotensin
(NTS) and cholecystokinin (CCK) inhibit lung cancer growth and increase the cytotoxicity of gefitinib. The results suggest
that GPCR transactivation of the EGFR may play an important role in cancer cell proliferation.
Keywords: Epidermal growth factor receptor, G protein-coupled receptor, lung cancer, non-peptide receptor antagonists, peptide
receptor agonists, transactivation of tyrosine kinase receptors.
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