RAC1 and cancer: We pursued this potential intervention with experiments using the small molecule EHOP-016,41,42 which is known to target and inhibit both RAC1 and RAC3, impeding the activity of the RAC downstream effector p21-activated kinase and cell migration in cancer cells.42 The HNSCC cell lines PE/CA-PJ 15 and HN6 are known to be resistant to cetuximab,43 and we confirmed as follows: at a cetuximab concentration of 50 μg/ml, only 13.65% and 12.64% of cells displayed proliferation defects (Fig. 7b and Supplementary Fig. 10b).