P-053 - MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Gastric Cancer
Translational Research
Presenter J. Wei
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors J. Wei, B. Liu, N. Wu, J. Shen, J. Du, X. Sun, Z. Lin
  • Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing/CN

Abstract

Introduction

Gastric cancer is among the leading causes of cancer deaths. Currently, only trastuzumab, ramucirumab, and lapatinib effectively treat gastric cancer. Thus, additional novel targets are required for this disease.

Methods

We investigated the immunohistochemical and fluorescence in situ hybridization expression of MET, ROS1, and ALK in four gastric cell lines and a cohort of 98 gastric cancer patients. Crizotinib response was studied using an in vitro histoculture drug response assay and the patient-derived GC xenograft model in vivo. Gene expression status was also analyzed for association with overall survival.

Results

Crizotinib potently inhibited in vitro cell growth in only one cell line, which also showed MET amplification. A positive correlation between crizotinib sensitivity and MET overexpression was observed (P = 0.045) in the histoculture drug response assay. Meanwhile, patient-derived tumor xenograft mouse models transplanted with tissues with higher MET protein expression displayed a highly selective sensitivity to crizotinib. In the 98 patients, MET overexpression was found in 42 (42.9%) and MET was amplified in 4 (4.1%). ROS1 and ALK overexpression were found in 25 (25.5%) and 0 patients, respectively. However, none of the patients screened harbored ALK or ROS1 rearrangements. There was no significant association found between overall survival and the MET or ROS1 status. We also observed a case that one advanced GC patient with MET-amplification experienced tumor shrinkage (PR by RECIST) after 3 weeks treated with crizotinib at the time of third-line chemotherapy failure. This patient also showed rapid clinical improvement, with decreased pain and improved performance status.

Conclusion

Crizotinib may induce clinically relevant anticancer effects in MET-overexpressing or -amplified gastric cancer patients.