C-Met inhibitors

C-Met inhibitors are a class of targeted cancer therapies that inhibit the activity of the C-Met receptor tyrosine kinase. The C-Met receptor, also known as the hepatocyte growth factor receptor (HGFR), plays a crucial role in various cellular processes, including proliferation, survival, and metastasis. Dysregulation of C-Met signaling is implicated in the progression of several types of cancer.

Mechanism of Action

C-Met inhibitors work by blocking the binding of the hepatocyte growth factor (HGF) to the C-Met receptor or by inhibiting the receptor's kinase activity. This inhibition prevents the activation of downstream signaling pathways, such as the PI3K/AKT/mTOR pathway and the RAS/RAF/MEK/ERK pathway, which are involved in cell growth and survival.

Types of C-Met Inhibitors

C-Met inhibitors can be classified into several categories based on their mechanism of action:

• Small molecule inhibitors: These compounds directly inhibit the kinase activity of the C-Met receptor. Examples include crizotinib, cabozantinib, and tivantinib.

• Monoclonal antibodies: These are antibodies designed to bind to the C-Met receptor or its ligand, HGF, thereby preventing receptor activation. Examples include onartuzumab and ficlatuzumab.

• Antibody-drug conjugates: These are monoclonal antibodies linked to cytotoxic drugs, which deliver the drug directly to C-Met expressing cells. An example is telisotuzumab vedotin.

Clinical Applications

C-Met inhibitors are primarily used in the treatment of various cancers, including:

• Non-small cell lung cancer (NSCLC)
• Renal cell carcinoma
• Hepatocellular carcinoma
• Gastric cancer

The effectiveness of C-Met inhibitors can vary depending on the presence of specific genetic mutations or amplifications in the C-Met gene.

Challenges and Future Directions

Despite their potential, the use of C-Met inhibitors faces several challenges, such as:

• Resistance: Tumors may develop resistance to C-Met inhibitors through various mechanisms, including secondary mutations or activation of alternative signaling pathways.

• Toxicity: Some C-Met inhibitors can cause significant side effects, which may limit their use in certain patient populations.

Future research is focused on overcoming these challenges by developing more selective inhibitors, combination therapies, and identifying biomarkers for patient selection.

Also see

• Tyrosine kinase inhibitors
• Targeted therapy
• Cancer treatment
• Monoclonal antibody therapy