EGFR Exon 20 Insertion Mutations in Sinonasal Squamous Cell Carcinoma

SIMPLE SUMMARY: The majority of patients with sinonasal squamous cell carcinoma (SNSCC) associated with inverted sinonasal papilloma carry an exon 20 insertion activating mutation in the epidermal growth factor receptor (EGFR). The aim of this review is to document the various features of EGFR mutations in SNSCC and other cancers, and to assess what we can learn from the study of these mutations in lung cancer, with a special focus on new therapeutic opportunities for SNSCC patients carrying EGFR exon 20 insertions mutations. ABSTRACT: Recurrent epidermal growth factor receptor (EGFR)-activating mutations have been identified in a rare form of head and neck cancer known as sinonasal squamous cell carcinoma (SNSCC), a malignant disease with a 5-year mortality rate of ~40%. Interestingly, the majority of EGFR mutations identified in patients with primary SNSCC are exon 20 insertions (Ex20ins), which is in contrast to non-small-cell lung cancer (NSCLC), where the EGFR exon 19 deletion and L858R mutations predominate. These studies demonstrate that EGFR Ex20ins mutations are not exclusive to lung cancer as previously believed, but are also involved in driving SNSCC pathogenesis. Here we review the landscape of EGFR mutations in SNSCC, with a particular focus on SNSCC associated with inverted sinonasal papilloma (ISP), a benign epithelial neoplasm. Taking lessons from NSCLC, we also discuss potential new treatment options for ISP-associated SNSCC harbouring EGFR Ex20ins in the context of targeted therapies, drug resistance and precision cancer medicine. Moving forward, further basic and translational work is needed to delineate the biology of EGFR Ex20ins in SNSCC in order to develop more effective treatments for patients with this rare disease.