EGFR and head and neck squamous cell carcinoma: Collectively, treatment-perturbation screens using targeted therapies such as mTOR inhibitors, EGFR inhibitors, glutamine inhibitors, and oHSV-1 have demonstrated the potential of synthetic-lethal approaches to treating HNSCC by mechanistically targeting mTOR signaling and cell-cycle regulation (INK128–palbociclib synergy), EGFR–PI3K pathway cross-talk (PIK3C2A-mediated TKI resistance), metabolic dependency on glutamine and ferroptosis regulators (GPX4), and epigenetic modulation of viral susceptibility via SUV39H2.