University of Chicago, Chicago, IL, USA.
J Clin Oncol. 2013 Mar 10;31(8):1089-96. doi: 10.1200/JCO.2012.43.9422. Epub 2013 Feb 11.
Lung cancer is a heterogeneous group of disorders that is now being subdivided into molecular subtypes with dedicated targeted therapies. The MET receptor tyrosine kinase has been identified as aberrantly overexpressed, potentially having activating mutations, and amplified in certain subsets of lung cancers. The ligand hepatocyte growth factor (HGF) can also be overexpressed in lung cancer or expressed in stroma, and both the MET receptor and the HGF ligand can be targets for therapeutics, especially in lung cancer. Activation of MET leads to a plethora of biochemical and biologic changes both in normal and cancerous cells. Preclinically, it has been shown that silencing or inactivating MET leads to decreased viability of cancer cells. There are a number of compounds against MET/HGF in clinical trials that have been shown to be active in lung cancers. This review will summarize the biology of MET as well as its therapeutic inhibition in lung cancer.
肺癌是一组异质性疾病，现在正被细分为具有特定靶向治疗的分子亚型。MET 受体酪氨酸激酶被确定为异常过表达，可能具有激活突变，并在某些肺癌亚群中扩增。配体肝细胞生长因子 (HGF) 也可以在肺癌中过度表达或在基质中表达，MET 受体和 HGF 配体都可以成为治疗的靶点，特别是在肺癌中。MET 的激活会导致正常和癌细胞中大量的生化和生物学变化。在临床前研究中，已经表明沉默或失活 MET 会导致癌细胞活力下降。目前有许多针对 MET/HGF 的化合物正在临床试验中，这些化合物已被证明对肺癌有效。这篇综述将总结 MET 的生物学及其在肺癌中的治疗抑制作用。
