2024 World Conference on Lung Cancer (WCLC) - Posters-P3.03I.05 DSTYK Inhibition as a Novel Strategy for Taxane-Based Chemotherapy Sensitation in Early and Advanced Lung Cancer

P3.03I.05 DSTYK Inhibition as a Novel Strategy for Taxane-Based Chemotherapy Sensitation in Early and Advanced Lung Cancer

Back to course

Pdf Summary

The study explores the impact of DSTYK inhibition on non-small cell lung cancer (NSCLC), particularly in enhancing the sensitivity of cancer cells to taxane-based chemotherapy. Despite chemotherapy being a standard treatment for lung cancer, resistance remains a significant challenge. The research highlights two main areas of need: discovering new therapeutic targets for tumors without known molecular alterations and expanding the efficacy of existing treatments.<br /><br />DSTYK, a kinase often amplified in cancers, was investigated for its role in lung cancer chemoresistance. The findings indicate that inhibiting DSTYK can sensitize NSCLC cells to taxanes like paclitaxel and docetaxel, paving the way for new treatment strategies.<br /><br />Key results include:<br /><br />1. **Increased Drug Sensitivity**: DSTYK depletion heightened sensitivity of lung cancer cells, specifically to taxane-based chemotherapy, as demonstrated in knockout models.<br /><br />2. **Cytoskeletal Remodeling and Metastasis Reduction**: Inhibition of DSTYK led to significant cytoskeletal changes, decreased adhesion, and reduced invasion capabilities. Metastatic potential was notably diminished in syngeneic mouse models with DSTYK knockout cells.<br /><br />3. **Therapeutic Potential**: Tumors with lower DSTYK levels responded better to a combined paclitaxel and carboplatin regimen. In mouse models, the combination of checkpoint inhibitors with this regimen fully eradicated DSTYK-deficient tumors, showcasing a synergistic effect.<br /><br />4. **Clinical Correlates**: Increased DSTYK copy number was associated with poorer pathological responses in patients undergoing combination therapy with paclitaxel, carboplatin, and αPD-1 inhibitors. This was validated through genomic analyses in clinical samples.<br /><br />Conclusively, DSTYK inhibition offers a promising strategy to enhance taxane-based chemotherapy efficacy in both early and advanced stages of lung cancer, potentially addressing resistance issues and guiding future therapeutic approaches.

Asset Subtitle

Luis Montuenga

Meta Tag

Speaker Luis Montuenga

Topic Tumor Biology – Translational Biology

Keywords

DSTYK inhibition

non-small cell lung cancer

NSCLC

taxane-based chemotherapy

chemoresistance

therapeutic targets

drug sensitivity

cytoskeletal remodeling

metastasis reduction

clinical correlates