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. 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. 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. Gefitinib appears to be most efficacious in treating certain EGFR gene mutations that are prevalent in Asian populations.
