Whole exome sequencing of cetuximab-resistant HNSCC cells. Study of genetic alterations in HNSCC cells upon acquired resistance to cetuximab

Anti-EGFR therapy (cetuximab) shows a limited clinical benefit for patients with locally advanced or recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), due to the frequent occurrence of secondary resistance mechanisms. A better understanding of resistance-causing mechanisms is crucial to develop new therapeutic strategies that may help improve response to cetuximab in HNSCC patients. Here, we carried out whole exome sequencing on cetuximab-sensitive HPV-negative HNSCC cell lines (FaDu, SCC22b and SC263) and matching cetuximab-resistant cell counterparts (established upon long-term exposure with the drug). This analysis revealed genetic alterations (i.e. genetic mutations and copy number variations) associated with acquired resistance to cetuximab in HNSCC cells.