Overall Christopher M, Kleifeld Oded
University of British Columbia Centre for Blood Research, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological & Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Nat Rev Cancer. 2006 Mar;6(3):227-39. doi: 10.1038/nrc1821.
The matrix metalloproteinases (MMPs) mediate homeostasis of the extracellular environment. They have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs. However, there are many criteria to consider in validating MMPs as drug targets and for the development of MMP inhibitors. The inhibition of some MMPs could have pro-tumorigenic effects (making them anti-targets), counterbalancing the benefits of target inhibition. These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?
基质金属蛋白酶（MMPs）介导细胞外环境的稳态。它们具有多种信号传导活性，在肿瘤发生过程中通常会发生改变，可能成为抗癌药物的干预靶点。然而，在将MMPs验证为药物靶点以及开发MMP抑制剂时，有许多标准需要考虑。抑制某些MMPs可能具有促肿瘤作用（使其成为反靶点），抵消了抑制靶点的益处。这些效应可能部分解释了MMP抑制剂在临床试验中的失败。MMP靶点验证和MMP抑制剂药物开发面临的主要挑战有哪些？
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