2024 World Conference on Lung Cancer (WCLC) - Posters-P3.03I.12 Modulation of EMT Increases the Activity of Lurbinectedin in Small Cell Lung Cancer

Pdf Summary

The study presented by Dr. Edurne Arriola at the Hospital del Mar Research Institute investigates the modulation of epithelial-to-mesenchymal transition (EMT) and its effects on the activity of lurbinectedin in small cell lung cancer (SCLC). Small cell lung cancer is characterized by a high degree of malignancy and is often resistant to conventional treatments such as chemotherapy and immunotherapy. The investigation particularly focuses on the HGF/MET pathway, a critical component in cancer progression and treatment resistance.<br /><br />The research utilized various human SCLC cell lines to explore the relationship between EMT states and response to lurbinectedin, a novel agent being evaluated for its efficacy in SCLC. The study determined the EMT state phenotype using different assays, such as RT-qPCR for SCLC subtype characterization, Western Blot for MET basal expression, RNA-seq data for EMT scoring, and cell viability assays to measure treatment response.<br /><br />Key findings demonstrate that cells with a mesenchymal phenotype (high EMT score) show increased sensitivity to lurbinectedin compared to epithelial phenotype cells. The study further analyzed the induction of phosphorylated MET (pMET) following HGF exposure and its subsequent impact on cell viability when combined with lurbinectedin and MET inhibitors. The experiments revealed that cells pre-treated with HGF, followed by lurbinectedin and/or MET inhibitor CP, showed altered viability, suggesting synergy between these treatments.<br /><br />In conclusion, modulating the EMT phenotype enhances the therapeutic efficacy of lurbinectedin in SCLC, indicating a potentially effective strategy for overcoming resistance to traditional chemotherapies. This research underscores the significance of targeting EMT and the HGF/MET pathway in developing more efficient treatment protocols for SCLC, although further investigation and clinical studies are warranted for validation.

Asset Subtitle

Edurne Arriola

Meta Tag

Speaker Edurne Arriola

Topic Tumor Biology – Translational Biology

Keywords

epithelial-to-mesenchymal transition

lurbinectedin

small cell lung cancer

HGF/MET pathway

treatment resistance

mesenchymal phenotype

phosphorylated MET

synergy

therapeutic efficacy

chemotherapy resistance