2023 World Conference on Lung Cancer (Posters)-P1.08. Exploring Autophagy Flux-Related Molecules for Overcoming EGFR TKI Resistance

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This abstract discusses the phenomenon of acquired drug resistance to EGFR TKIs (tyrosine kinase inhibitors) in non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. The study aimed to identify autophagy flux-related signaling molecules that may be closely associated with acquired resistance in mEGFR NSCLC.<br /><br />The researchers established resistant sub-cell lines through prolonged exposure to Osimertinib and Erlotinib, two common EGFR TKIs. They then analyzed the protein expressions of autophagy flux molecules and explored genes that induce autophagy flux activity. They also evaluated the protein expression of autophagy flux-related signaling molecules using immunohistochemistry.<br /><br />The results showed that autolysosomes were accumulated in the resistant sub-cell lines, along with increased protein expression of LC3B and p62. Autophagy flux-related signaling molecules, including BECLIN1, GABAR1, NBR1, PINK1, and ULK1, were significantly increased in the resistant cells. In patients with mEGFR NSCLC, the expression of CAGE, p-AMPK, p-Beclin1, and ULK1 was significantly higher compared to wild-type EGFR NSCLC.<br /><br />The findings suggest that autophagy flux-related signaling molecules and known genetic variants are strongly associated with resistance acquired during EGFR TKI treatment in mEGFR NSCLC patients. The researchers are currently conducting additional functional studies of the identified autophagy-related genes to explore their potential as targets for overcoming EGFR TKI resistance.<br /><br />In summary, this study provides evidence that autophagy flux-related signaling molecules play a role in acquired resistance to EGFR TKIs in mEGFR NSCLC patients. Understanding these mechanisms could potentially lead to the development of targeted therapies to overcome drug resistance in this patient population.

Asset Subtitle

Jin-Hyoung Kang

Meta Tag

Speaker Jin-Hyoung Kang

Topic Tumor Biology: Translational Biology - Drug Resistance

Keywords

acquired drug resistance

EGFR TKIs

non-small cell lung cancer

NSCLC

activating EGFR mutations

autophagy flux-related signaling molecules

mEGFR NSCLC

Osimertinib

Erlotinib

protein expressions