Holiday Notification: Cayman Chemical will be closed Monday, May 28, 2012, in observance of the Memorial Day holiday.
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Overactivity of the epidermal growth factor receptor-associated tyrosine kinase (EGFR-TK) has been associated with a number of cancers and thus TK inhibitors could be potential therapeutic agents to prevent malignant growth.1 Gefitinib is a selective EGFR-TK inhibitor that blocks the growth of GEO colon cancer, ZR-75-1 and MCF-10A Ha-ras breast cancer, and OVCAR-3 ovarian cancer cell lines with IC50s ranging between 0.2-0.4 µM.2 By interfering with the intracellular kinase domain, gefitinib prevents EGFR autophosphorylation and prevents downstream signal transduction. Gefitinib has been used to treat advanced (or recurrent) non-small cell lung cancer. However, the FDA retracted its general approval for this compound (Iressa™) when a phase III trial failed to demonstrate an overall survival benefit.3 Gefitinib appears to be most efficacious in treating certain EGFR gene mutations that are prevalent in Asian populations.4,5
1
Sausville, E.A., Elsayed, Y., Monga, M., et al. Signal transduction-directed cancer treatments. Annu Rev Pharmacol Toxicol43199-231(2003).
2
Ciardiello, F., Caputo, R., Bianco, R., et al. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res62053-2063(2000).
3
Gerber, D.E. EGFR inhibition in the treatment of non-small cell lung cancer. Drug Dev Res69(6)359-372(2008).
4
Yang, C., Hung, J., Lai, C., et al. Gefitinib as first-line therapy for advanced or metastatic non-small cell lung cancer patients in southern Taiwan. Kaohsiung J Med Sci26(1)1-7(2010).
5
Uruga, H., Kishi, K., Fujii, T., et al. Efficacy of gefitinib for elderly patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor gene mutations: A retrospective analysis. Intern Med49103-107(2010).
Yang, C., Hung, J., Lai, C., et al. Gefitinib as first-line therapy for advanced or metastatic non-small cell lung cancer patients in southern Taiwan. Kaohsiung J Med Sci26(1)1-7(2010).
Sausville, E.A., Elsayed, Y., Monga, M., et al. Signal transduction-directed cancer treatments. Annu Rev Pharmacol Toxicol43199-231(2003).
Ciardiello, F., Caputo, R., Bianco, R., et al. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res62053-2063(2000).
Gerber, D.E. EGFR inhibition in the treatment of non-small cell lung cancer. Drug Dev Res69(6)359-372(2008).
Uruga, H., Kishi, K., Fujii, T., et al. Efficacy of gefitinib for elderly patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor gene mutations: A retrospective analysis. Intern Med49103-107(2010).