| Title |
Overexpression of PI3K p110α contributes to acquired resistance to MET inhibitor, in MET-amplified SNU-5 gastric xenografts
|
|---|---|
| Published in |
Drug Design, Development and Therapy, October 2015
|
| DOI | 10.2147/dddt.s89410 |
| Pubmed ID | |
| Authors |
Fujian Ji, Xuanwen Liu, Yuanyu Wu, Xuedong Fang, Guomin Huang |
| Abstract |
Gastric cancer is one of the most virulent malignant diseases and is the second leading cause of cancer mortality in the world. The receptor tyrosine kinase MET is constitutively activated in many gastric cancers and its expression is strictly required for survival of some gastric cancer cells. Targeting gastric cancers with amplified or abnormally activated MET may have therapeutic benefit based on nonclinical and emerging clinical findings. However, one of the major problems of therapies targeting tyrosine kinases is that many tumors are not responsive to treatment or eventually develop resistance to the drugs. This study aims to understand the mechanisms of MET resistance in gastric SNU-5 xenografts which developed resistance to PHA665752, a MET inhibitor, through long-period tyrosine kinase inhibitor exposure. In the current study, we found that PI3K p110α is overexpressed in PHA665752-resistant SNU-5 xenografts. These findings showed that high PI3K p110α expression contributes to tyrosine kinase inhibitor resistance. In addition, we reported the development of a carcinogen-induced gastric cancer model that recapitulates PI3K p110α expression in human disease, which will serve as a useful model to study PI3K p110α's biology and its effectiveness as a novel biomarker and a molecular target for gastric cancer. Ultimately, PI3K p110α represents a novel target for gastric cancer. |
Mendeley readers
The data shown below were compiled from readership statistics for 8 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 8 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 2 | 25% |
| Student > Bachelor | 1 | 13% |
| Researcher | 1 | 13% |
| Student > Postgraduate | 1 | 13% |
| Unknown | 3 | 38% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 50% |
| Agricultural and Biological Sciences | 1 | 13% |
| Biochemistry, Genetics and Molecular Biology | 1 | 13% |
| Unknown | 2 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 October 2015.
All research outputs
#22,760,732
of 25,374,917 outputs
Outputs from Drug Design, Development and Therapy
#1,754
of 2,268 outputs
Outputs of similar age
#245,758
of 286,877 outputs
Outputs of similar age from Drug Design, Development and Therapy
#86
of 110 outputs
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