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Published on: July 21, 2018
Targeting the MET pathway for potential treatment of NSCLC
Anna Li1, Hong-Fei Gao, Yi-Long Wu
1Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Science , 106 Zhongshan 2nd Road, Guangzhou 510080 , PR China +86 20 83877855 ; +86 20 83827712 ; syylwu@live.cn.
Introduction:
The mesenchymal-epithelial transition (MET) protein is the only known receptor for hepatocyte growth factor and has recently been identified as a novel promising target in several human cancers, including NSCLC. Activation of the MET signaling pathway can occur via different mechanisms. A number of compounds targeting MET have been evaluated in clinical trials, and recent clinical data have begun to afford some insight into the tumor types and patient populations that might benefit from treatment with MET pathway inhibitors.
Areas Covered:
We review recent publications and information disclosed at public conferences and summarize the epidemiology of dysregulation of MET signaling, and the associations thereof with other driver genes and therapeutic inhibitors useful to treat NSCLC.
Expert Opinion:
The MET pathway is emerging as a target for advanced NSCLC that is either resistant to EGFR tyrosine kinase inhibitors or that arises de novo. MET inhibitors currently being evaluated in clinical trials have yielded compelling evidence of clinical activities when used to treat various solid tumors, especially NSCLC. Remaining challenges are the identification of patient populations who might benefit from the use of MET inhibitors, and the most effective diagnostic methods for such patients.
Insights
The MET pathway is a promising target for non-small cell lung cancer (NSCLC), particularly for resistant or de novo cases. MET inhibitors show clinical activity, but identifying optimal patient populations and diagnostic methods remains key.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- The mesenchymal-epithelial transition (MET) protein, a receptor for hepatocyte growth factor, is a novel target in human cancers like non-small cell lung cancer (NSCLC).
- MET signaling pathway activation can occur through various mechanisms.
- Compounds targeting MET have undergone clinical trials, with emerging data on patient benefit.
Purpose of the Study:
- To review the epidemiology of MET signaling dysregulation in NSCLC.
- To summarize associations with other driver genes and therapeutic inhibitors.
- To provide insight into patient populations benefiting from MET pathway inhibitors.
Main Methods:
- Review of recent publications.
- Analysis of information disclosed at public conferences.
Main Results:
- The MET pathway is a target for advanced NSCLC, including EGFR tyrosine kinase inhibitor-resistant or de novo cases.
- MET inhibitors in clinical trials demonstrate significant clinical activity in various solid tumors, especially NSCLC.
- Compelling evidence of clinical activity for MET inhibitors in NSCLC.
Conclusions:
- The MET pathway is an emerging therapeutic target for advanced NSCLC.
- MET inhibitors show promise, particularly in EGFR-TKI resistant or de novo NSCLC.
- Challenges include identifying optimal patient populations and diagnostic strategies for MET inhibitor therapy.
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