Successful Treatment with Crizotinib to Overcome Drug Resistance Possibly Due to Mesenchymal-epithelial Transition Amplification in a Lung Cancer Patient with the Echinoderm Microtubule-associated Protein-like 4-anaplastic Lymphoma Kinase Fusion Gene

Amplification of the mesenchymal-epithelial transition (MET) gene plays an important role in anticancer drug resistance to anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-rearranged lung cancer cells. We encountered an ALK-rearranged lung cancer patient who developed MET amplification after alectinib treatment and showed an effective response to fifth-line crizotinib. First-line alectinib treatment was effective for 2.5 years; however, liver metastases exacerbated. Liver biopsy specimens revealed MET and human epidermal growth factor receptor 2 (HER2) amplifications. Switching to the MET inhibitor crizotinib improved liver metastases. Crizotinib may be effective in ALK-positive patients with MET amplification.

 

Comments：

It highlights the importance of genetic testing and personalized treatment approaches for lung cancer patients with ALK rearrangements.

 

The amplification of the MET gene has been shown to play a significant role in the development of resistance to ALK-TKIs in EML4-ALK-rearranged lung cancer cells. In this case, the patient developed MET amplification after treatment with alectinib, which resulted in the progression of liver metastases. The detection of MET and HER2 amplifications in liver biopsy specimens further supports the role of genetic testing in guiding treatment decisions for lung cancer patients.

Switching to crizotinib, a MET inhibitor, was effective in improving liver metastases in this patient. This suggests that crizotinib may be a viable treatment option for ALK-positive patients with MET amplification. It is important to note that the patient had received four lines of treatment prior to crizotinib, highlighting the need for continued research into treatment options for patients with advanced lung cancer.

Overall, this case report underscores the importance of personalized treatment approaches based on genetic testing for lung cancer patients with ALK rearrangements, and the potential for MET inhibitors like crizotinib in treating patients with MET amplification.

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S2762	Alectinib	Alectinib is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429.

Related Targets

ALK