西妥昔单抗
表皮生长因子受体
免疫疗法
医学
癌症研究
受体酪氨酸激酶
单克隆抗体
表皮生长因子受体抑制剂
MAPK/ERK通路
PI3K/AKT/mTOR通路
酪氨酸激酶
免疫系统
信号转导
受体
免疫学
内科学
抗体
生物
细胞生物学
作者
James Kang,Albert I. Ko,Sang Hoon Kil,Jon Mallen–St. Clair,Daniel Sanghoon Shin,Marilene B. Wang,Eri S. Srivatsan
标识
DOI:10.1016/j.bbcan.2022.188827
摘要
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.
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