RETRACTED: AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Malignant pleural mesothelioma (MPM) is a lethal cancer lacking targeted therapies.
• Single receptor tyrosine kinase (RTK) inhibitors have shown limited efficacy in MPM.
• Investigating AXL and MET receptor roles is crucial for novel therapeutic strategies.

Purpose of the Study:

• To evaluate the expression and potential gene amplification of AXL and MET receptors in MPM.
• To assess the efficacy of AXL and MET multitarget inhibitors in MPM cells.
• To identify a potential subset of MPM patients who could benefit from combined AXL and MET inhibition.

Main Methods:

• Immunohistochemistry and Fluorescence in situ hybridization (FISH) on MPM tissue samples.
• In vitro studies to correlate receptor expression with sensitivity to multitarget inhibitors.
• Analysis of AXL and MET co-expression, gene amplification, and ligand expression.

Main Results:

• Co-expression of AXL and MET receptors was observed in 10.4% of MPM cases, independent of ligand expression or gene amplification.
• In vitro studies indicated that combined AXL and MET inhibition impacts MPM cell proliferation and aggressiveness.
• The study identified a potential correlation between AXL-MET co-activation and response to multitarget inhibitors.

Conclusions:

• A subset of MPM patients exhibits AXL and MET co-activation.
• Combined pharmacological inhibition of AXL and MET shows promise in reducing MPM cell proliferation and aggressiveness.
• MPM patients with AXL-MET co-activation may benefit from multitargeted therapies inhibiting both receptors.