Kelsey Leinweber - Acquired Resistance in NSCLC Cells Presentation

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      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.

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