EGFR pathway targeting drugs in head and neck cancer in the era of immunotherapy

Receptor tyrosine kinases (RTKs) are cell surface receptors that bind growth factor ligands and initiate cellular signaling. Of the 20 classes of RTKs, 7 classes, I-V, VIII, and X, are linked to head and neck cancers (HNCs). We focus on the first class of RTK, epidermal growth factor receptor (EGFR), as it is the most thoroughly studied class. EGFR overexpression is observed in 20% of tumors, and expression of EGFR variant III is seen in 15% of aggressive chemoradiotherapy resistant HNCs. Currently, the EGFR monoclonal antibody (mAb) cetuximab is the only FDA approved RTK-targeting drug for the treatment of HNCs. Clinical trials have also included EGFR mAbs, with tyrosine kinase inhibitors, and small molecule inhibitors targeting the EGFR, MAPK, and mTOR pathways. Additionally, Immunotherapy has been found to be effective in 15 to 20% of patients with recurrent or metastatic HNC as a monotherapy. Thus, attempts are underway for the combinatorial treatment of immunotherapy and EGFR mAbs to determine if the recruitment of immune cells in the tumor microenvironment can overcome EGFR resistance.

Automated summary

Receptor tyrosine kinases (RTKs) are cell surface receptors that bind growth factor ligands and initiate cellular signaling. Among the 20 classes of RTKs, 7 classes are linked to head and neck cancers (HNCs). The epidermal growth factor receptor (EGFR) is the most studied class of RTK, with overexpression observed in 20% of tumors and a variant III expression seen in 15% of aggressive chemoradiotherapy resistant HNCs. Current treatments include EGFR monoclonal antibodies and inhibitors targeting the EGFR, MAPK, and mTOR pathways, with immunotherapy showing effectiveness in a subset of patients with HNC. Combination therapy of immunotherapy and EGFR monoclonal antibodies is being explored to overcome EGFR resistance.