Lin et al. (2019) showed SMAD4 knockdown tumor cell lines were more viable and inhibited cell apoptosis when treated with cetuximab in comparison to cells with overexpression of SMAD4. Similar findings were observed in somatic SMAD4 loss of head and neck squamous cell carcinoma, conferring resistance to cetuximab therapy (Ozawa et al., 2017). This evidence concerns the gene SMAD4 and head and neck squamous cell carcinoma.