2023 World Conference on Lung Cancer (Posters)-EP12.01. Anlotinib Combined with Osimertinib Reverses Acquired Osimertinib Resistance in NSCLC by Targeting the c-MET/MYC/AXL Axis

EP12.01. Anlotinib Combined with Osimertinib Reverses Acquired Osimertinib Resistance in NSCLC by Targeting the c-MET/MYC/AXL Axis - PDF(Abstract)

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This study investigated the combination of anlotinib and osimertinib as a potential treatment for non-small cell lung cancer (NSCLC) patients with EGFR mutations who have acquired resistance to osimertinib. Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI), but drug resistance limits its efficacy. The researchers conducted in vitro and in vivo experiments to explore the effects of combined treatment with anlotinib and osimertinib on osimertinib resistance in NSCLC cells. They also investigated the underlying molecular mechanism behind its anti-tumor effects.<br /><br />The results showed that the combination of anlotinib and osimertinib effectively overcame clinical resistance in a patient who experienced slow progression after second-line osimertinib therapy. In vitro and in vivo experiments confirmed the synergistic anti-tumor effects of the combination treatment in NSCLC cells. The researchers found that AXL played a role in conferring resistance to osimertinib, and anlotinib enhanced anti-tumor efficacy by inhibiting AXL in NSCLC cell lines. They also discovered that MYC binds to the promoter of AXL, promoting its transcription, and that the combination therapy inactivated the c-MET/MYC/AXL axis in NSCLC, leading to enhanced anti-tumor effects.<br /><br />In conclusion, the study demonstrated that the combination of anlotinib and osimertinib exerted synergistic anti-tumor effects by targeting the c-MET/MYC/AXL axis. These findings provide a theoretical basis for the clinical application of this combination therapy.

Asset Subtitle

Zhaoxia Wang

Meta Tag

Speaker Zhaoxia Wang

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

anlotinib

osimertinib

non-small cell lung cancer

NSCLC

EGFR mutations

drug resistance

tyrosine kinase inhibitor

in vitro

in vivo

anti-tumor effects