Although the critical role of EGFR-Arf1 in HDAC-targeted treatment has been demonstrated in culture HNSCC cells, prospective studies are warranted to provide evidence showing the difference of EGFR-Arf1 activity in clinical metastatic and non-metastatic HNSCC samples and their correlation with the therapeutic efficacy of HDAC inhibitors. The gene discussed is ARF1; the disease is head and neck squamous cell carcinoma.