Building on our previous findings, where MEK inhibition via trametinib demonstrated efficacy in treating HNSCC [17], this study extended its investigation to include not only the molecular alterations underlying these effects but also the role of oncogenic MYC in modulating HNSCC vulnerability to MEK inhibition with trametinib in in vitro and in vivo settings. The gene discussed is MAP2K7; the disease is head and neck squamous cell carcinoma.