Yegodayev et al. demonstrated a similar relationship between CAFs and mitigated efficacy of cetuximab in HNSCC, but also went further to show that TGF-β signaling was implicated in this association, and that blocking the TGF-β pathway using the SMAD3 inhibitor SIS3 enhanced cetuximab efficacy in PDX models. This evidence concerns the gene TGFB1 and head and neck squamous cell carcinoma.