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Targeting the c-MET signaling pathway for cancer therapy
Xiangdong Liu1, Wenqing Yao, Robert C Newton
1Incyte Corporation, Experimental Station, Rt. 141 & Henry Clay Road, Wilmington, DE 19880, USA. xliu@incyte.com
Background:
In many human cancers, c-MET is activated via receptor overexpression, amplification, mutation and/or a ligand-dependent autocrine/paracrine loop. These biochemical and genetic abnormalities have been correlated with poor clinical outcomes and drug resistance in cancer patients. Preclinical studies suggest that targeting aberrant c-MET signaling could be an attractive therapy in cancer, but this notion has only recently been tested in the clinic.
Objectives:
To describe the biological aspects of the c-MET signaling pathway and to discuss recent progress and possible future trends in the development of agents that target the c-MET pathway, with an emphasis on small-molecule c-MET kinase inhibitors.
Method:
A review of relevant publications, including published articles in literature, reports at scientific meetings, and information available through the Internet.
Results/Conclusion:
The dysregulated c-MET pathway represents a promising target for cancer drug development. The agents that target the c-MET pathway have demonstrated impressive evidence of early clinical activity and may have a significant therapeutic potential.
Insights
Targeting the c-MET signaling pathway, often overactive in cancers, shows promise. Small-molecule inhibitors targeting c-MET kinase are demonstrating early clinical activity and therapeutic potential in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- c-MET signaling pathway dysregulation is common in human cancers.
- Aberrant c-MET activation correlates with poor prognosis and drug resistance.
- Targeting c-MET is a potential therapeutic strategy in oncology.
Purpose of the Study:
- To review the biological mechanisms of c-MET signaling.
- To discuss the progress of c-MET pathway-targeting agents.
- To highlight small-molecule c-MET kinase inhibitors.
Main Methods:
- Literature review of scientific publications.
- Analysis of scientific meeting reports.
- Information synthesis from internet resources.
Main Results:
- Early clinical trials show promising activity for c-MET inhibitors.
- The c-MET pathway is a viable target for novel cancer therapies.
- Small-molecule inhibitors are advancing in clinical development.
Conclusions:
- Dysregulated c-MET signaling presents a significant therapeutic target in cancer.
- Agents targeting the c-MET pathway exhibit notable early clinical efficacy.
- These agents hold substantial potential for cancer treatment.
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