Two studies mapped genes essential for HNSCC cell proliferation and survival [13,14]; two specifically interrogated cisplatin resistance [15,16]; one study investigated radiation resistance [17]; and three focused on synthetic-lethal targets, covering vulnerabilities to mTOR [18] or EGFR [19] or glutamine metabolism [20] inhibitors/antagonists and a host determinant of oncolytic HSV-1 (oHSV-1) [21] efficacy, respectively. Here, EGFR is linked to head and neck squamous cell carcinoma.