The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth
The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth
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DOI：
10.1038/nrc2130
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发表时间：
2007-05-01
影响因子：
78.5
通讯作者：
Yancopoulos, George D.
中科院分区：
文献类型：
--
作者：
Thurston, Gavin;Noguera-Troise, Irene;Yancopoulos, George D.
抗血管生成疗法已成为几种肿瘤的重要治疗选择。迄今为止，这些疗法主要集中在阻断血管内皮生长因子（VEGF）途径。最近的一系列论文表明，Notch受体的一个配体，δ样配体4 (DLL4)，通常由VEGF诱导，是一种抑制血管发芽和分支的负反馈调节剂。与这一作用一致，DLL4的缺失或抑制导致过度的非生产性血管生成。这种不受约束的血管生成出人意料地和矛盾地减少肿瘤生长，甚至在抗vegf治疗的肿瘤中也是如此。过多的血管生成是否对肿瘤有害而对患者有益？
Anti-angiogenesis therapies have emerged as important treatment options for several types of tumours. To date, these therapies have focused on blocking the vascular endothelial growth factor ( VEGF) pathway. A recent series of papers have shown that one ligand for the Notch receptors, Delta-like ligand 4 ( DLL4), is normally induced by VEGF and is a negative- feedback regulator that restrains vascular sprouting and branching. Consistent with this role, the deletion or inhibition of DLL4 results in excessive, non- productive angiogenesis. This unrestrained angiogenesis unexpectedly and paradoxically decreases tumour growth, even in tumours resistant to anti-VEGF therapies. Can too much angiogenesis be bad for tumours but good for patients?