Murphy Gillian
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
Nat Rev Cancer. 2008 Dec;8(12):929-41. doi: 10.1038/nrc2459. Epub 2008 Nov 13.
Over the last few years disintegrin metalloproteinases of the Adam (a disintegrin and metalloproteinase) family have been associated with the process of proteolytic 'shedding' of membrane-associated proteins and hence the rapid modulation of key cell signalling pathways in the tumour microenvironment. Furthermore, numerous members of the Adam family have been associated with tumorigenesis and tumour progression. The question now arises of whether pharmacological manipulation of their functions would be a useful adjunct to therapies targeting intercellular communications. To learn from the lessons of matrix metalloproteinase inhibitors as anticancer agents, there are many facets of the biological and clinical relevance of the ADAMs that need to be understood before embarking with confidence on such an approach.
在过去几年中，Adam（一种去整合素和金属蛋白酶）家族的去整合素金属蛋白酶已与膜相关蛋白的蛋白水解“脱落”过程相关联，从而与肿瘤微环境中关键细胞信号通路的快速调节相关。此外，Adam家族的众多成员已与肿瘤发生和肿瘤进展相关联。现在出现的问题是，对其功能进行药理学操纵是否会成为针对细胞间通讯的治疗方法的有用辅助手段。为了从基质金属蛋白酶抑制剂作为抗癌药物的经验中吸取教训，在满怀信心地采用这种方法之前，需要了解ADAMs生物学和临床相关性的许多方面。
