George Washington University Hospital, Washington, DC, United States.
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, United States.
Adv Cancer Res. 2020;147:259-301. doi: 10.1016/bs.acr.2020.04.006. Epub 2020 Jun 17.
First discovered in the 1984, the MET receptor tyrosine kinase (RTK) and its ligand hepatocyte growth factor or HGF (also known as scatter factor or SF) are implicated as key players in tumor cell migration, proliferation, and invasion in a variety of cancers. This pathway also plays a key role during embryogenesis in the development of muscular and nervous structures. High expression of the MET receptor has been shown to correlate with poor prognosis and resistance to therapy. MET exon 14 splicing variants, initially identified by us in lung cancer, is actionable through various tyrosine kinase inhibitors (TKIs). For this reason, this pathway is of interest as a therapeutic target. In this chapter we will be discussing the history of MET, the genetics of this RTK, and give some background on the receptor biology. Furthermore, we will discuss directed therapeutics, mechanisms of resistance, and the future of MET as a therapeutic target.
MET 受体酪氨酸激酶（RTK）及其配体肝细胞生长因子或 HGF（也称为分散因子或 SF）于 1984 年首次发现，其被认为是多种癌症中肿瘤细胞迁移、增殖和侵袭的关键因素。该途径在胚胎发生过程中肌肉和神经结构的发育中也起着关键作用。已有研究表明，MET 受体的高表达与预后不良和治疗耐药性相关。MET 外显子 14 剪接变体最初是在肺癌中由我们鉴定的，可通过各种酪氨酸激酶抑制剂（TKI）进行靶向治疗。出于这个原因，该途径作为治疗靶点引起了人们的兴趣。在这一章中，我们将讨论 MET 的历史、该 RTK 的遗传学，并提供有关受体生物学的一些背景知识。此外，我们将讨论定向治疗、耐药机制以及 MET 作为治疗靶点的未来。
