Analysis of cetuximab-induced gene expression changes in head and neck squamous cell carcinoma cell lines

Despite recent advances in immunotherapy and anti-epidermal growth factor receptor (EGFR) treatments, the therapeutic landscape for locally advanced HNSCC has changed little over recent decades, and clinical outcome remains poor. Cetuximab, monoclonal antibody targeting EGFR, offers only modest and often transient clinical responses, 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. To uncover early transcriptional adaptations to EGFR inhibition, we performed bulk RNA-sequencing on FaDu and HN5 HNSCC cells treated with cetuximab for 72 hours.