Sainson Richard C A, Harris Adrian L
Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Trends Mol Med. 2007 Sep;13(9):389-95. doi: 10.1016/j.molmed.2007.07.002. Epub 2007 Sep 6.
Since the early 1970s, the dogma postulating that blocking tumour angiogenesis can inhibit tumour growth has been accepted widely and has resulted in the generation of a variety of successful anti-angiogenic therapies. More recently, new signalling pathways, such as the Dll4-Notch signalling pathway, have been shown to regulate angiogenesis during development. In pathological conditions, such as cancer, Dll4 is up-regulated strongly in the tumour vasculature. Based on this expression pattern, different molecules have been generated to block Dll4 signalling. Unexpectedly, these blocking agents inhibited tumour growth in vivo by triggering excessive but nonfunctional angiogenesis. Altogether, these molecules constitute a new category of pro-angiogenic yet anticancer agents and offer an exciting alternative to previously described vascular targeting molecules.
自20世纪70年代初以来，认为阻断肿瘤血管生成可抑制肿瘤生长的教条已被广泛接受，并催生了多种成功的抗血管生成疗法。最近，新的信号通路，如Dll4-Notch信号通路，已被证明在发育过程中调节血管生成。在诸如癌症等病理条件下，Dll4在肿瘤血管系统中强烈上调。基于这种表达模式，已研发出不同分子来阻断Dll4信号。出乎意料的是，这些阻断剂通过引发过度但无功能的血管生成在体内抑制肿瘤生长。总之，这些分子构成了一类新的促血管生成但抗癌的药物，并为先前描述的血管靶向分子提供了令人兴奋的替代方案。
