2024 World Conference on Lung Cancer (WCLC) - Posters-P3.02G.01 Therapeutic Targeting of Lung Cancer-Associated Fibroblasts Mitigates Mediastinal Lymphatic Dissemination in Non-Small Cell Lung Cancer

P3.02G.01 Therapeutic Targeting of Lung Cancer-Associated Fibroblasts Mitigates Mediastinal Lymphatic Dissemination in Non-Small Cell Lung Cancer

Back to course

Pdf Summary

The study "Therapeutic Targeting of Lung Cancer-Associated Fibroblasts Mitigates Mediastinal Lymphatic Dissemination in Non-Small Cell Lung Cancer" by James CM Ho and Caoyang Chen investigates the role of cancer-associated fibroblasts (CAFs) in non-small cell lung cancer (NSCLC) and their potential as therapeutic targets to prevent metastasis, specifically to mediastinal lymph nodes. CAFs are a significant component of the tumor microenvironment and are known to facilitate tumor progression and metastasis, although their specific role in mediastinal lymphatic dissemination in NSCLC had not been fully elucidated.<br /><br />To address this gap, the researchers developed novel orthotopic xenograft models using NSCLC cell lines (H358 and HCC827) cocultured with lung CAFs. These models allowed for the testing of two potential therapeutic agents: ABT-199 and NNMTi (Nicotinamide N-Methyltransferase inhibitor). ABT-199 administration resulted in notable reductions in tumor growth, lymphangiogenesis, collagen deposition, and mediastinal lymph node metastasis in the H358-CAFs-rich model. Similarly, NNMTi effectively reduced tumor burden, proliferation, and lymphangiogenesis in the HCC827-CAFs-rich model.<br /><br />The results highlight the role of lung CAFs in promoting tumoral lymphangiogenesis and metastasis to mediastinal lymph nodes in NSCLC. Targeting CAFs, therefore, emerges as a promising strategy for hindering cancer spread through the lymphatic system, particularly in CAFs-rich NSCLC cases. Both ABT-199 and NNMTi show potential as therapeutic agents in this respect, offering pathways for further research and development in NSCLC treatment.

Asset Subtitle

James HO

Meta Tag

Speaker James HO

Topic Tumor Biology – Preclinical Biology

Keywords

non-small cell lung cancer

cancer-associated fibroblasts

mediastinal lymphatic dissemination

tumor microenvironment

orthotopic xenograft models

ABT-199

NNMTi

tumoral lymphangiogenesis

metastasis

therapeutic targets