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Taxotere Induces Dephosphorylation of MET in Patient-derived Tumor Models
Hyemin Mun1, Sun-Hye Lee1, Chu-Hee Lee2
1Department of Biomedical Sciences, The University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Background/Aim:
Although molecular targeting therapy is an attractive treatment for cancer, resistance eventually develops in most cases. Here, we evaluated chemotherapeutic efficacy on non-small cell lung cancer (NSCLC) with acquired resistance to epidermal growth factor receptor inhibitors mechanistically.
Materials And Methods:
Antitumor effects of taxotere were evaluated using multiple models, including xenograft, and patient-derived models developed from adenocarcinoma cancer patients. Protein expressions were analyzed after drug treatment.
Results:
Taxotere inhibited tumor growth of NSCLC cells harboring drug resistance, and reduced the expression of phosphorylated MET proto-oncogene, receptor tyrosine kinase (MET). A tumor-inhibitory effect of taxotere was also demonstrated in vivo in xenografts in mice, patient-derived primary lung tumor cells and patient-derived xenograft with concomitant repression of phosphorylated MET expression. Chemotherapeutic and MET-targeting drug exhibited a synergistic cell growth-inhibitory effect.
Conclusion:
These results suggest that the anticancer drug taxane may be an adjuvant for lung tumors exhibiting enhanced signaling of MET networks.
Insights
Chemotherapy drug taxane effectively inhibits non-small cell lung cancer (NSCLC) with acquired resistance to epidermal growth factor receptor inhibitors. Taxane also reduces MET signaling, suggesting its potential as an adjuvant therapy for lung tumors with enhanced MET networks.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Acquired resistance to molecular targeting therapies like epidermal growth factor receptor inhibitors is a significant challenge in non-small cell lung cancer (NSCLC) treatment.
- Understanding the mechanisms of resistance is crucial for developing effective alternative or combination therapies.
Purpose of the Study:
- To investigate the chemotherapeutic efficacy of taxane in NSCLC models with acquired resistance to epidermal growth factor receptor inhibitors.
- To elucidate the underlying molecular mechanisms, particularly focusing on MET proto-oncogene, receptor tyrosine kinase (MET) signaling.
Main Methods:
- Antitumor effects of taxotere were evaluated in various NSCLC models, including xenografts and patient-derived models.
- Protein expression analysis, specifically of phosphorylated MET, was performed after drug treatment.
Main Results:
- Taxotere demonstrated significant inhibition of tumor growth in drug-resistant NSCLC cells and in vivo models.
- Treatment with taxotere led to reduced expression of phosphorylated MET.
- A synergistic cell growth-inhibitory effect was observed when combining taxane with a MET-targeting drug.
Conclusions:
- The anticancer drug taxane shows promise as an effective treatment for NSCLC that has developed resistance to epidermal growth factor receptor inhibitors.
- Taxane may serve as an adjuvant therapy for lung tumors characterized by enhanced MET signaling pathways.
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