Kang James J, Ko Albert, Kil Sang Hoon, Mallen-St Clair Jon, Shin Daniel Sanghoon, Wang Marilene B, Srivatsan Eri S
Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA.
Department of Surgery, VA Greater Los Angeles Healthcare System/UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
Biochim Biophys Acta Rev Cancer. 2023 Jan;1878(1):188827. doi: 10.1016/j.bbcan.2022.188827. Epub 2022 Oct 27.
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.
受体酪氨酸激酶（RTKs）是细胞表面受体，可结合生长因子配体并启动细胞信号传导。在20类RTKs中，有7类，即I-V类、VIII类和X类，与头颈癌（HNCs）相关。我们聚焦于第一类RTK，即表皮生长因子受体（EGFR），因为它是研究最为深入的一类。在20%的肿瘤中观察到EGFR过表达，在15%侵袭性放化疗耐药的HNCs中可见EGFR变体III的表达。目前，EGFR单克隆抗体（mAb）西妥昔单抗是唯一获得美国食品药品监督管理局（FDA）批准用于治疗HNCs的靶向RTK药物。临床试验还包括了EGFR单克隆抗体、酪氨酸激酶抑制剂以及靶向EGFR、丝裂原活化蛋白激酶（MAPK）和雷帕霉素靶蛋白（mTOR）途径的小分子抑制剂。此外，免疫疗法已被发现作为单一疗法对15%至20%复发或转移性HNC患者有效。因此，正在尝试将免疫疗法与EGFR单克隆抗体联合治疗，以确定肿瘤微环境中免疫细胞的募集是否能够克服EGFR耐药性。
