Evaluation of cetuximab-induced gene expression changes in residual PDX tumors of head and neck squamous cell carcinoma

Cetuximab, a monoclonal antibody targeting EGFR, offers only modest and often transient clinical responses in recurrent or metastatic HNSCC, owing to the persistence of a therapy-tolerant cell population that seeds residual disease and eventual therapeutic failure. Clinical evidence across cancer types indicates that depth of response to targeted therapy correlates with prolonged progression-free survival, highlighting the importance of residual disease as a driver of resistance. However, the molecular features enabling HNSCC cells to tolerate EGFR blockade before the acquisition of stable resistance remain incompletely understood. We analyzed residual tumors from cetuximab-treated patient-derived xenograft (PDX) models of HNSCC (#UCLHN04 and #HNC004) to identify gene expression changes associated with anti-EGFR tolerance in HNSCC cells.