Drug Resistance Of Gefitinib In Non-small-cell Lung Cancer Treatment

The molecule targeted therapy of tumor is a brand new therapy that has developed recently. Gefitinib is the first target drug in the treatment of advanced stage non-small-lung cancer(NSCLC),and has characteristics of high specificity,quick efficacy and low adverse effect.It can inhibit the activity of epidermal growth factor receptor(EGFR) tyrosine kinase to block the transmembrane signal transduction.In that way,gefitinib can inhibit the dysplasia and metastasis of tumor cells.There are some relationships between the clinical efficacy and EGFR gene mutations.In some patients,this therapy has been successful initially,but the truth is that gefitinib designed to inhibit tyrosine kinase can not completely eradicate these tumors due to the development of drug resistance.The drug resistance can be divided into primary resistance and secondary resistance.In current state,what has known about mechanisms of primary resistance include K-ras mutations,loss of PTEN functions and a novel G796A mutation in exon 20 of EGFR.In human lung adenocarcinomas with EGFR mutation,a second-site point mutation that substitutes methionine for threonine at position 790(T790M) is associated with approximately half of cases of secondary resistance to gefitinib.Other mechanisms that contribute to gefitinib secondary resistance include EGFR receptor internalization and MET gene amplification.It becomes more clearly that several molecular mechainsms have been suggested to contribute to the drug resistance.A number of strategies to overcome drug resistance are currently being tested.While primary resistance and secondary resistance will continue to be a problem,what we have learned so far has paved the way for overcoming these problems.