Kim Ki-Hyun, Kim Hyori
Cancer Research Institute, College of Medicine, Seoul National University, Jongno-gu, Seoul, Republic of Korea.
Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University, Jongno-gu, Seoul, Republic of Korea.
Exp Mol Med. 2017 Mar 24;49(3):e307. doi: 10.1038/emm.2017.17.
Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials. However, to date none of these HGF/cMET inhibitors have shown significant efficacy in clinical trials. Furthermore, no receptor tyrosine kinase inhibitors primarily targeting cMET have been approved. Given that neutralization of HGF or cMET does not cause significant adverse effects, inhibition of the HGF/cMET signaling pathway appears to be safe. In this review, we summarized the completed and ongoing clinical trials testing antibody- or protein-based anticancer drugs targeting cMET and HGF.
人类癌细胞中失调的受体酪氨酸激酶信号传导会导致肿瘤进展、侵袭和转移。受体酪氨酸激酶cMET在癌组织中经常过度表达，cMET信号的激活与耐药性以及致癌、侵袭和转移过程有关。因此，cMET及其配体肝细胞生长因子（HGF）被认为是抗癌药物开发的主要靶点。至少有8种抗cMET抗体和4种抗HGF抗体已在临床试验中进行测试或正在进行测试。然而，迄今为止，这些HGF/cMET抑制剂在临床试验中均未显示出显著疗效。此外，尚无主要靶向cMET的受体酪氨酸激酶抑制剂获得批准。鉴于中和HGF或cMET不会引起明显的不良反应，抑制HGF/cMET信号通路似乎是安全的。在本综述中，我们总结了针对cMET和HGF的基于抗体或蛋白质的抗癌药物的已完成和正在进行的临床试验。
