Drug development against metastasis-related genes and their pathways: a rationale for cancer therapy.
Drug development against metastasis-related genes and their pathways: a rationale for cancer therapy.
复制标题
DOI：
10.1016/j.bbcan.2008.07.002
复制
发表时间：
2008-12
影响因子：
11.2
通讯作者：
Watabe, Kounosuke
中科院分区：
文献类型：
--
作者：
Iiizumi, Megumi;Liu, Wen;Pai, Sudha K.;Furuta, Eiji;Watabe, Kounosuke
关键词：
众所周知，大多数癌症相关死亡是由转移性疾病引起的。因此，迫切需要开发特异性靶向转移过程的治疗性干预。在过去的十年中，这一研究领域取得了重大进展，出现了许多新的概念，阐明了转移级联的分子机制，通常被描述为六个不同的步骤：局部侵袭，内渗，易位，外渗，微转移和定植。成功的转移依赖于每个步骤中转移促进因子和抑制因子的平衡和复杂的相互作用。因此，我们干预的基本策略旨在阻断这种疾病过程中的启动子或增强抑制子。为了实现这一目标，已经设计了各种抗体和小分子。这些包括阻断转移促进剂的配体-受体相互作用（HGF/c-Met）、拮抗转移促进酶（AMF、uPA和MMP）和抑制转移促进剂的转录活性（β-连环蛋白）的药剂。另一方面，转移抑制因子及其信号通路的有趣作用已被广泛研究，并已进行了各种尝试来增强这些因子。已经开发了小分子来恢复转移抑制基因的表达或模拟其功能，如NM 23、E-cadherin、Kiss-1、MKK 4和NDRG 1，其中一些正在进行临床试验。本文综述了肿瘤转移的分子途径，并讨论了抗转移药物的策略和最新进展。
It is well recognized that the majority of cancer related deaths is caused by metastatic disease. Therefore, there is an urgent need for the development of therapeutic intervention specifically targeted to the metastatic process. In the last decade, significant progress has been made in this research field, and many new concepts have emerged that shed light on the molecular mechanism of metastasis cascade which is often portrayed as a succession of six distinct steps; localized invasion, intravasation, translocation, extravasation, micrometastasis and colonization. Successful metastasis is dependent on the balance and complex interplay of both the metastasis promoters and suppressors in each step. Therefore, the basic strategy of our interventions is aimed at either blocking the promoters or potentiating the suppressors in this disease process. Toward this goal, various kinds of antibodies and small molecules have been designed. These include agents that block the ligand-recepter interaction of metastasis promoters (HGF/c-Met), antagonize the metastasis promoting enzymes (AMF,uPA and MMP) and inhibit the transcriptional activity of metastasis promoter (β-Catenin). On the other hand, the intriguing roles of metastasis suppressors and their signal pathways have been extensively studied and various attempts have been made to potentiate these factors. Small molecules have been developed to restore the expression or mimic the function of metastasis suppressor genes such as NM23, E-cadherin, Kiss-1, MKK4 and NDRG1, and some of them are under clinical trials. This review summarizes our current understanding of the molecular pathway of tumor metastasis and discusses strategies and recent development of anti-metastatic drugs.
登录
查看更多内容
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Boccaccio, C;Sabatino, G;Comoglio, PM
通讯作者：
Comoglio, PM
影响因子：
25.7
作者：
Behari, Jaideep;Zeng, Gang;Monga, Satdarshan P. S.
通讯作者：
Monga, Satdarshan P. S.
影响因子：
4.8
作者：
Ammanamanchi, S;Brattain, MG
通讯作者：
Brattain, MG
影响因子：
2.8
作者：
Alikunju, Shanavas;Pillarisetti, Sivaram
通讯作者：
Pillarisetti, Sivaram