Targeting MET Amplification: Opportunities and Obstacles in Therapeutic Approaches

SIMPLE SUMMARY: The MET gene is crucial for cell growth and has shown promise as a cancer treatment target. However, distinguishing between focal amplification and polysomy, different types of gene multiplication, is challenging. Accurate differentiation requires techniques such as in situ hybridization (ISH) or next generation sequencing (NGS). As the effectiveness of MET inhibitors can vary, careful patient selection and defining the perfect amplification threshold are critical. Future studies should focus on determining optimal therapy combinations and innovating new treatments targeting MET amplification. ABSTRACT: The MET gene plays a vital role in cellular proliferation, earning it recognition as a principal oncogene. Therapies that target MET amplification have demonstrated promising results both in preclinical models and in specific clinical cases. A significant obstacle to these therapies is the ability to distinguish between focal amplification and polysomy, a task for which simple MET copy number measurement proves insufficient. To effectively differentiate between the two, it is crucial to utilize comparative measures, including in situ hybridization (ISH) with the centromere or next generation sequencing (NGS) with adjacent genes. Despite the promising potential of MET amplification treatment, the judicious selection of patients is paramount to maximize therapeutic efficacy. The effectiveness of MET inhibitors can fluctuate depending on the extent of MET amplification. Future research must seek to establish the ideal threshold value for MET amplification, identify the most efficacious combination therapies, and innovate new targeted treatments for patients exhibiting MET amplification.