Publication Details (including relevant citation information):
Part of the 2012 Chemistry Lecture Series at Regis University. Regis University had 6 Lectures throughout the year and this one was the only one given by a student. All other lecturers were professional Chemists.
Major causes of lung cancer are mutations of the epidermal growth factor receptor (EGFR) and the rat sarcoma (Ras) gene (26). The Ras gene codes for the production of Ras proteins; proteins that signal the cells to divide and grow at appropriate times. When there is a mutation or damage to this gene, cancerous activity can develop. The Ras proteins act as binary switches that bind GDP in the allosteric site and GTP in their active site (34). When oncogenes are created, cell signaling occurs without a ligand, causing uncontrollable growth. Gefitnib is a tyrosine kinase inhibitor (TKI) targeting EGFR. Mutations in the EGFR kinase domain occur early, during development, and are generally unrelated to smoking whereas Ras mutations are normally smoking-related (13). Mutations in EGFR lead to unregulated cell differentiation, proliferation, and allow for tumor growth.By chronically adapting cell lines to be resistant to TKIs, we may be able to find a way around the resistance. If we can identify what the resistance mechanism is, we can target the already resistant cells with other drug therapies.FGFR-dependent Colo699 NSCLC cells that have been adapted to grow in high concentrations of an FGFR inhibitor express high levels of HGF and use the MET receptor tyrosine kinase as a dominant growth driver. My growth experiments demonstrate that the adapted cells have become very sensitive to a MET-specific tyrosine kinase inhibitor.