Targeting the c-Met signaling pathway in cancer.
Targeting the c-Met signaling pathway in cancer.
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DOI：
10.1158/aacr.edb-ccr-06-0818
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发表时间：
2008-04
期刊：
影响因子：
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通讯作者：
B. Peruzzi;D. Bottaro
中科院分区：
文献类型：
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作者：
B. Peruzzi;D. Bottaro
肝细胞生长因子 (HGF) 与细胞表面受体酪氨酸激酶 (TK)（称为 c-Met）结合后，可刺激多种细胞靶标的有丝分裂、运动发生和形态发生，包括上皮细胞和内皮细胞、造血细胞、神经元、黑素细胞和肝细胞。这些多效性作用在发育、体内平衡和组织再生过程中至关重要。 HGF 信号传导还有助于多种人类癌症的肿瘤发生和肿瘤进展，并促进与肿瘤转移密切相关的侵袭性细胞侵袭。我们目前对 c-Met 致癌信号传导的理解支持至少三种途径选择性抗癌药物开发途径：拮抗配体/受体相互作用、抑制 TK 催化活性以及阻断细胞内受体/效应器相互作用。已经使用所有这三种策略开发了有效的、选择性的临床前候选药物，并且这三个领域中的两个领域的人体临床试验正在进行中。
On binding to the cell surface receptor tyrosine kinase (TK) known as c-Met, hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of cellular targets including, epithelial and endothelial cells, hematopoietic cells, neurons, melanocytes, and hepatocytes. These pleiotropic actions are fundamentally important during development, homeostasis, and tissue regeneration. HGF signaling also contributes to oncogenesis and tumor progression in several human cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis. Our present understanding of c-Met oncogenic signaling supports at least three avenues of pathway selective anticancer drug development: antagonism of ligand/receptor interaction, inhibition of TK catalytic activity, and blockade of intracellular receptor/effector interactions. Potent and selective preclinical drug candidates have been developed using all three strategies, and human clinical trials in two of the three areas are now under way.