Su et al. employed HNSCC patient-derived organoids to demonstrate that chemotherapy-resistant CAFs promote drug resistance via Transforming Growth Factor Alpha (TGFα)-Epidermal Growth Factor Receptor (EGFR) paracrine signaling, thereby activating Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (AKT)/p65 to suppress p53/caspase-3-mediated apoptosis. This evidence concerns the gene AKT1 and head and neck squamous cell carcinoma.