Department of Tumor Biology and Angiogenesis, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature. 2010 Feb 11;463(7282):E6-7. doi: 10.1038/nature08751.
Delta-like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target for cancer therapy. However, the potential side effects of blocking this pathway remain uncertain. Here we show that chronic DLL4 blockade causes pathological activation of endothelial cells, disrupts normal organ homeostasis and induces vascular tumours, raising important safety concerns.
Delta-like 4(DLL4)介导的 Notch 信号通路已成为癌症治疗的一个有吸引力的靶点。然而,阻断这条通路的潜在副作用仍不确定。在这里,我们表明慢性 DLL4 阻断会导致内皮细胞的病理性激活,破坏正常的器官内稳态,并诱导血管肿瘤,引发重要的安全问题。