Interaction Between EGFR Mutation S768I And EGFR Tyrosine Kinase Inhibitors

Background:Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Advances in the knowledge of molecular mechanisms of carcinogenesis have promoted the development of many novel molecular-targeted agents including the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). And it has been certain that EGFR-TKIs have its clear advantages in NSCLC patients with sensitive mutation in EGFR such as L858R to Traditional chemotherapy. While most patients get the drug resistance with a secondary mutation of EGFR(T790M). And as in the same exon namely exon20as the T790M mutation, S768I is not so resistance to TKIs as that. As the S768I mutation is not studied that much, this article will find out whether the S768I mutation is sensitive or resistance to the TKIs through clinical and protein researches.Patients and Methods:We reviewed data from5125consecutive patients with lung cancer whose tumors underwent EGFR mutation testing. And identify24patients with S768I mutation in EGFR. Patient characteristics including age,sex, smoking history, stage, treatment history, and overall survival were collected. At the same time, we get the S768I and wildtype EGFR protein expressed in SF9cells. And we determined the affinity between2kinds of TKIs (gefitinib and erlotinib) and either the S768I or wildtype EGFR respectively.Results:There were36.2%patients with EGFR mutations (1854/5125). And among the whole5125patients,3053cases were male(59.6%), and2072female(40.4%). Patient ages ranged from5to91years old with the median age of59years old. Cancer forms were identified in1177of patients tested:977samples were adenocarcinomas while only200were squamous cell carcinomas. And there were24patients with the S768I mutation, the ratio is1.22%(24/1854) among all EGFR mutations. And80.8%(17/24) S768I mutation combine with one other EGFR mutation.2of the S768I mutation cases were used Iressa, and both of them were TNM stage IV NSCLC with the mutation G719X/S768I. One of them got partial remission(PR) after using TKI for6months, while ended the treatment as to the resistance. The other one died after1month by the TKI treatment. In the meanwhile, we determined the affinity between Gefitinib and S768I as11nM, Gefitinib and wildtype EGFR as18nM, Erlotinib and S768I as2.2nM, Erlotinib and wildtype EGFR as2.6nM.Conclusion:S768I mutation occupies1.22%among whole EGFR mutation patients. The S768I mutation has the stronger affinity than that of wildtype EGFR. The Gefitinib can be a good treatment for S768I mutation patients with its dose reasonable increased.