A Paired Tumor Organoid-Stroma Biobank Reveals PLAU⁺ Fibroblasts as Drivers of Chemoresistance in Lung Adenocarcinoma.

PLAU⁺ fibroblasts drive chemoresistance in lung adenocarcinoma by activating a CXCL5-CLGN pathway, with high CLGN levels linked to poor patient survival.

• Why it matters: Understanding the mechanisms behind chemoresistance in LUAD is crucial for improving treatment outcomes, as current therapies often fail to eliminate tumors effectively.
• What they did: A biobank of patient-derived LUAD organoids and fibroblasts was created, revealing that CAFs expressing PLAU reduce drug sensitivity and induce tumor cell resistance through a specific signaling axis.
• The result: Targeting CLGN restored drug sensitivity in resistant tumors, indicating that inhibiting this pathway could offer a new therapeutic approach to overcome chemoresistance in advanced LUAD.