Kuhnert Frank, Kirshner Jessica R, Thurston Gavin
Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Vasc Cell. 2011 Sep 18;3(1):20. doi: 10.1186/2045-824X-3-20.
Tumor angiogenesis is an important target for cancer therapy, with most current therapies designed to block the VEGF signaling pathway. However, clinical resistance to anti-VEGF therapy highlights the need for targeting additional tumor angiogenesis signaling pathways. The endothelial Notch ligand Dll4 (delta-like 4) has recently emerged as a critical regulator of tumor angiogenesis and thus as a promising new therapeutic anti-angiogenesis target. Blockade of Dll4-Notch signaling in tumors results in excessive, non-productive angiogenesis with resultant inhibitory effects on tumor growth, even in some tumors that are resistant to anti-VEGF therapies. As Dll4 inhibitors are entering clinical cancer trials, this review aims to provide current perspectives on the function of the Dll4-Notch signaling axis during tumor angiogenesis and as a target for anti-angiogenic cancer therapy.
肿瘤血管生成是癌症治疗的一个重要靶点，目前大多数治疗方法旨在阻断血管内皮生长因子（VEGF）信号通路。然而，抗VEGF治疗的临床耐药性凸显了靶向其他肿瘤血管生成信号通路的必要性。内皮Notch配体Dll4（类Delta样蛋白4）最近已成为肿瘤血管生成的关键调节因子，因此是一个有前景的新型抗血管生成治疗靶点。阻断肿瘤中的Dll4-Notch信号会导致过度的、无效的血管生成，从而对肿瘤生长产生抑制作用，即使在一些对抗VEGF治疗耐药的肿瘤中也是如此。随着Dll4抑制剂进入癌症临床试验，本综述旨在就Dll4-Notch信号轴在肿瘤血管生成过程中的功能以及作为抗血管生成癌症治疗靶点提供当前的观点。
