Patient-derived malignant effusion organoids guide tailored therapy and dissect third-generation EGFR-tyrosine kinase inhibitor resistance mechanisms in lung cancer - PubMed
7 hours ago
- #lung-cancer
- #drug-resistance
- #organoids
- Lung cancer is the leading cause of cancer-related mortality, with drug resistance being a major treatment challenge.
- An optimized protocol was developed to create patient-derived organoids (PDOs) from malignant effusion samples, achieving an 82.8% success rate.
- PDOs effectively predicted clinical treatment responses with 91.7% specificity, 71.4% sensitivity, and 87.1% overall accuracy.
- Transcriptomic analysis identified key pathways (ECM remodeling, cell cycle dysregulation, angiogenesis) involved in EGFR-TKI resistance.
- Ibuprofen was identified as a candidate to enhance osimertinib's anti-tumor activity and overcome resistance, validated in PDOs and cell models.
- The study provides new insights into EGFR-TKI resistance and offers tools for precision treatment and personalized drug screening in advanced lung cancer.