2021 Targeted Therapies of Lung Cancer (TTLC) Meeting - Posters-P09. Restoring Therapeutic Efficacy of Osimertinib in EGFR-driven NSCLC by Targeting the BMP/Endoglin Signaling Axis

P09. Restoring Therapeutic Efficacy of Osimertinib in EGFR-driven NSCLC by Targeting the BMP/Endoglin Signaling Axis - PDF

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Researchers from Cedars-Sinai Medical Center in Los Angeles have identified a potential strategy to restore the therapeutic efficacy of Osimertinib, a targeted therapy for non-small cell lung cancer (NSCLC) driven by mutations in the epidermal growth factor receptor (EGFR). While Osimertinib has shown dramatic efficacy in NSCLC, resistance often develops within two years of treatment. The study aimed to improve the effectiveness of Osimertinib by targeting the BMP/Endoglin signaling axis.<br /><br />The researchers established an Osimertinib-resistant cell line called H1975R from NSCLC cells that harbored EGFR mutations. By co-culturing the NSCLC cells with lung fibroblasts, the researchers found that the presence of fibroblasts reduced the efficacy of Osimertinib. However, when a monoclonal antibody called carotuximab, which blocks BMP signaling, was combined with Osimertinib, the response to Osimertinib improved.<br /><br />Through single-cell RNA sequencing, the researchers observed that the Osimertinib-resistant cells exhibited greater expression of bypass signaling factors and small cell markers. Carotuximab treatment led to a significant downregulation of these markers. In xenograft models, the combination therapy of carotuximab and Osimertinib reduced tumor expansion compared to either drug alone or the control.<br /><br />The results suggest that the tumor microenvironment plays a key role in determining cellular outcomes to Osimertinib in NSCLC. The study provides a potential treatment strategy for NSCLC patients who develop resistance to Osimertinib by targeting the BMP/Endoglin signaling axis with carotuximab. Further research is needed to validate these findings and explore the clinical potential of this combination therapy.

Asset Subtitle

Manish Thiruvalluvan

Meta Tag

Speaker Manish Thiruvalluvan

Topic Targeted Therapies - EGFR

Keywords

Cedars-Sinai Medical Center

Osimertinib

non-small cell lung cancer

NSCLC

epidermal growth factor receptor

EGFR mutations

BMP/Endoglin signaling axis

Osimertinib-resistant cell line

carotuximab

tumor microenvironment