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July 9, 2026Cancer Cell InternationalOpen Access

ANGPTL4 contributes to osimertinib resistance through NDRG1-associated extracellular matrix remodeling in EGFR-mutant NSCLC organoid models

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Authors

DZDai-Yan ZhouPXPei XieSWS S Wang

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Overview

Randomized trial investigates ANGPTL4's role in osimertinib resistance in EGFR-mutant NSCLC, suggesting new therapeutic avenues.

Key Points

  • This study aims to elucidate the role of ANGPTL4 in osimertinib resistance in EGFR-mutant non-small cell lung cancer.
  • Established a 3D osimertinib-resistant organoid model to mimic the tumor microenvironment.
  • Employed transcriptome sequencing and bioinformatics for identifying key resistance mediators.
  • Conducted functional experiments including knockdown and overexpression of ANGPTL4 and NDRG1.
  • ANGPTL4 was significantly upregulated in osimertinib-resistant organoids, reducing drug sensitivity.
  • Knockdown of ANGPTL4 restored osimertinib sensitivity in resistant models, whereas overexpression promoted resistance.
  • NDRG1 interaction with ANGPTL4 was crucial for extracellular matrix pathway activation, supporting its role in drug resistance.

Cite This Study

Zhou et al. (2026) studied this question.

synapsesocial.com/papers/6a4f3c8a2b81a944af575de9https://doi.org/10.1186/s12935-026-04400-5
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