Targeting epidermal growth factor receptor--are we missing the mark?

摘要: Context: Aberrant signalling through the epidermal growth factor receptor (EGFR) is associated with neoplastic cell prolification, migration, sromal invasion,resistance to apoptosis, and angiogenesis The high frequency of abnormalities in EGFR human carcinomass gliomass taboratory studies showing that inhibition can impair tumour means an attractive target for developement cancer therapeutics, Among classes agents targeting clinical are monocional antibodies against extracellular ligamd-binding domain receptor, small molecules inhibit activation tyrosine kinase. Although these pharmacological mechanistic differences between two inhibitor, preclinical suggest they both proliferation have additive or synergistic cytotoxicity stnadard therapies Results from early tests indicate well tolerated anti-tumour activity. Starting point: May, 2003, Astralian Therapeutic Goods Administration US Food Drug approved inhibitor gefitinib (201899, Iressa) treatment patients advanced non-small-cell lung (NSCLC) previously treated chemotherapy. approval has based on results a phase 2 study 210 NScLC, including 142 refractorydisease. In this subgroup response rate was about 10%. drug granted despite negative randomised controlled trials over 2000 untreated NSCLC, which showed no benefit survival survival, objective responses, time progression when getitinib added Where next? Research needed identify validate. predictive factors be used select disease likely respond inhibitors, elucidate mechanism interaction standard other moleculary targetted agents. Appropriately designed trial required define optimum dose, schedule, sequence combination conventional targted