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c-MET 作为癌症治疗靶点和生物标志物的研究进展

c-MET as a potential therapeutic target and biomarker in cancer.

机构信息

Princess Margaret Hospital/Ontario Cancer Institute and University of Toronto, Toronto, Ontario, Canada.

出版信息

Ther Adv Med Oncol. 2011 Nov;3(1 Suppl):S21-35. doi: 10.1177/1758834011422557.

DOI:10.1177/1758834011422557
PMID:22128285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3225018/
Abstract

The receptor tyrosine kinase c-MET and its ligand, hepatocyte growth factor (HGF), regulate multiple cellular processes that stimulate cell proliferation, invasion and angiogenesis. This review provides an overview of the evidence to support c-MET or the HGF/c-MET signaling pathway as relevant targets for personalized cancer treatment based on high frequencies of c-MET and/or HGF overexpression, activation, amplification in non-small cell lung carcinoma (NSCLC), gastric, ovarian, pancreatic, thyroid, breast, head and neck, colon and kidney carcinomas. Additionally, the current knowledge of small molecule inhibitors (tivantinib [ARQ 197]), c-MET/HGF antibodies (rilotumumab and MetMAb) and mechanisms of resistance to c-MET-targeted therapies are discussed.

摘要

受体酪氨酸激酶 c-MET 和其配体肝细胞生长因子(HGF)调节多种细胞过程,刺激细胞增殖、侵袭和血管生成。这篇综述提供了支持 c-MET 或 HGF/c-MET 信号通路作为非小细胞肺癌(NSCLC)、胃癌、卵巢癌、胰腺癌、甲状腺癌、乳腺癌、头颈部癌、结肠癌和肾癌中基于 c-MET 和/或 HGF 过表达、激活、扩增的个体化癌症治疗相关靶点的证据概述。此外,还讨论了小分子抑制剂(tivantinib [ARQ 197])、c-MET/HGF 抗体(rilotumumab 和 MetMAb)以及对 c-MET 靶向治疗的耐药机制的最新知识。

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本文引用的文献

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Semaphorin 4D, a lymphocyte semaphorin, enhances tumor cell motility through binding its receptor, plexinB1, in pancreatic cancer.神经信号素 4D 是一种淋巴细胞神经信号素,通过与其受体 plexinB1 结合增强胰腺癌肿瘤细胞的运动性。
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Favorable response to crizotinib in three patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion-type oncogene-positive non-small cell lung cancer.三例棘皮动物微管相关蛋白样 4-间变性淋巴瘤激酶融合型癌基因阳性非小细胞肺癌患者对克唑替尼的良好反应。
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ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity.ALK 融合基因阳性肺癌及 3 例 ALK 激酶活性抑制剂治疗病例。
Lung Cancer. 2012 Jan;75(1):66-72. doi: 10.1016/j.lungcan.2011.05.027. Epub 2011 Jul 14.
4
Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification.克唑替尼(PF02341066)的活性,一种双重间质-上皮转化(MET)和间变性淋巴瘤激酶(ALK)抑制剂,在一个新出现 MET 扩增的非小细胞肺癌患者中。
J Thorac Oncol. 2011 May;6(5):942-6. doi: 10.1097/JTO.0b013e31821528d3.
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Quantitative phospho-proteomic profiling of hepatocyte growth factor (HGF)-MET signaling in colorectal cancer.定量磷酸化蛋白质组学分析肝癌生长因子(HGF)-MET 信号在结直肠癌中的作用。
J Proteome Res. 2011 Jul 1;10(7):3200-11. doi: 10.1021/pr200238t. Epub 2011 Jun 9.
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Gene amplification and protein overexpression of MET are common events in ovarian clear-cell adenocarcinoma: their roles in tumor progression and prognostication of the patient.MET 基因扩增和蛋白过表达在卵巢透明细胞腺癌中较为常见:它们在肿瘤进展和患者预后中的作用。
Mod Pathol. 2011 Aug;24(8):1146-55. doi: 10.1038/modpathol.2011.70. Epub 2011 Apr 8.
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Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer.电离辐射诱导 MET 的表达及其在肿瘤放射抵抗和侵袭生长中的作用。
J Natl Cancer Inst. 2011 Apr 20;103(8):645-61. doi: 10.1093/jnci/djr093. Epub 2011 Apr 4.
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Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target.MET 扩增对胃癌的影响:作为一种新型预后标志物和潜在治疗靶点的可能作用。
Oncol Rep. 2011 Jun;25(6):1517-24. doi: 10.3892/or.2011.1219. Epub 2011 Mar 18.
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Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies.ARQ 197 是一种选择性 c-MET 抑制剂的 I 期临床试验,包含了作用机制的药效动力学研究的证据。
J Clin Oncol. 2011 Apr 1;29(10):1271-9. doi: 10.1200/JCO.2010.31.0367. Epub 2011 Mar 7.
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The association between EGFR variant III, HPV, p16, c-MET, EGFR gene copy number and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.头颈部复发或转移性鳞状细胞癌患者中表皮生长因子受体(EGFR)III型变体、人乳头瘤病毒(HPV)、p16、c-间质-上皮转化因子(c-MET)、EGFR基因拷贝数与EGFR抑制剂反应之间的关联。
Head Neck Oncol. 2011 Feb 27;3:11. doi: 10.1186/1758-3284-3-11.