Although RAS is known to play a key role in innate resistance to a variety of therapeutics used in SCCs, including platinum-based chemotherapy and anti-EGFR antibodies [43,66], and HRAS inactivation sensitizes HNSCC PDX tumors to a range of drugs in mice (Figure 3), it has been established that much of the documented antineoplastic activity of FTIs is mediated by effects on proteins other than RAS [71,72]. Here, EGFR is linked to head and neck squamous cell carcinoma.