Crizotinib-Resistant MET Mutations in Gastric Cancer Patients are Sensitive to Type II Tyrosine Kinase Inhibitors

Aim: Crizotinib has been used to counter MET amplification in different human malignancies. However, transient responses were observed in some patients with rapid acquisition of resistant mutations in MET. Materials&methods:MET mutations stably expressed Ba/F3 cell lines were used for IC50 detection. Signaling pathway analysis was done using 293T cell line. Results: Four MET mutations conferred resistance to crizotinib with sustained activation of downstream signaling pathways of MET. On the other hand, the four MET mutations displayed different response to type II tyrosine kinase inhibitors with variable deterioration of the downstream signals. Conclusion: This study suggested that patients carrying MET V1092L, D1228G or Y1230H mutations could benefit from type II tyrosine kinase inhibitor treatment, but not patients with G1163R or D1228Y/N mutations.