Patient-derived organoids from resected non-small cell lung cancers for personalized high-throughput response testing with approved and repurposed drugs

The five-year survival for localized non-small cell lung cancer (NSCLC) patients undergoing curative surgery remains ~50% largely due to recurrence. Patient-derived organoids (PDOs) have high potential as clinically relevant high-throughput drug testing platforms to treat NSCLC. Treatment response of PDOs to carboplatin/paclitaxel was determined by growth differences versus vehicle group. 5/10 (50%) PDOs were chemo-sensitive, whereas 5/10 (50%) PDOs were chemo-resistant. Whole transcriptome analysis revealed conservation of epithelial cell signatures in all PDOs and upregulation of aldoketoreductases (AKR1B10/15) in chemo-resistant PDOs . AKR1B10 inhibitory drug epalrestat was repurposed and effectively sensitized the chemoresistance PDOs to carboplatin/paclitaxel.