In the clinic: ongoing clinical trials evaluating c-MET-inhibiting drugs

• Main Authors: Neelesh Sharma, Alex A. Adjei
• Format: Article
• Language: English
• Published: SAGE Publishing 2011-11-01
• Series: Therapeutic Advances in Medical Oncology
• Online Access: https://doi.org/10.1177/1758834011423403

The c-MET (mesenchymal–epithelial transition factor) pathway is dysregulated in many human cancers and promotes tumor growth, invasion and dissemination. The c-MET receptor tyrosine kinase can be activated via gene mutation, gene amplification, protein overexpression and/or a ligand-dependent autocrine/paracrine loop. Abnormalities in c-MET signaling have been reported to correlate with poor clinical outcomes and drug resistance in patients with cancer. Significant progress has been made in advancement of c-MET pathway inhibitors through to clinical trials. A robust pipeline of high-quality inhibitors targeting different aspects of c-MET activation is currently being explored in phase I, II and III clinical trials across multiple tumor types. Preliminary data demonstrate promising clinical activity with these agents, along with an acceptable toxicity profile. In this manuscript, the pharmacological profile of drugs targeting the c-MET pathway and available data from ongoing clinical trials of these drugs are discussed.