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Gastric Cancer. 2016 Jul;19(3):778-88. doi: 10.1007/s10120-015-0545-5. Epub 2015 Sep 24.

MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer.

Author information

1
The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
2
Pangaea Biotech, USP Dexeus University Institute, Barcelona, Spain.
3
Department of General Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
4
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Medical Oncology Service, Badalona, Spain.
5
The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China. weijia01627@hotmail.com.

Abstract

BACKGROUND:

Currently, only trastuzumab, ramucirumab, and apatinib 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 in vitro and in vivo.

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. No significant association was found between overall survival and MET or ROS1 status. We also observed a stage IV gastric cancer patient with MET amplification who experienced tumor shrinkage and clinical benefit after 3 weeks of crizotinib as fourth-line treatment.

CONCLUSIONS:

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

KEYWORDS:

ALK; Crizotinib; MET; ROS1

PMID:
26404902
DOI:
10.1007/s10120-015-0545-5
[Indexed for MEDLINE]

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