Cantelmo Anna Rita, Pircher Andreas, Kalucka Joanna, Carmeliet Peter
a Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology , KU Leuven , Leuven , Belgium.
b Laboratory of Angiogenesis and Vascular Metabolism , Vesalius Research Center, Center for Cancer Biology (CCB), VIB , Leuven , Belgium.
Expert Opin Ther Targets. 2017 Mar;21(3):239-247. doi: 10.1080/14728222.2017.1282465. Epub 2017 Jan 27.
Antiangiogenic drugs were originally designed to starve tumors by cutting off their vascular supply. Unfortunately, when these agents are used as monotherapy or in combination with chemotherapy, they provide only modest survival benefits in the order of weeks to months in most cancer patients. Strategies normalizing the disorganized tumor vasculature offer the potential to increase tumor perfusion and oxygenation, and to improve the efficacy of radio-, chemo- and immunotherapy, while reducing metastasis. Areas covered: This review discusses tumor vascular normalization (TVN) as an alternative strategy for anti-angiogenic cancer treatment. We summarize (pre)-clinical strategies that have been developed to normalize tumor vessels as well as their potential to enhance standard therapy. Notably, we describe how targeting endothelial cell metabolism offers new possibilities for antiangiogenic therapy through evoking TVN. Expert opinion: Several drugs targeting VEGF signaling are now clinically used for antiangiogenic cancer treatment. However, excessive blood vessel pruning impedes perfusion and causes tumor hypoxia, known to promote cancer cell dissemination and impair radio-, chemo- and immunotherapy. Normalized vessels lessen tumor hypoxia, impair cancer cell intravasation and enhance anticancer treatment. New data indicate that targeting endothelial cell metabolism is an alternative strategy of antiangiogenic cancer treatment via promotion of TVN.
抗血管生成药物最初旨在通过切断肿瘤的血管供应来使其饥饿。不幸的是，当这些药物作为单一疗法或与化疗联合使用时，在大多数癌症患者中，它们仅能提供数周至数月的适度生存益处。使紊乱的肿瘤血管正常化的策略有可能增加肿瘤灌注和氧合，并提高放疗、化疗和免疫治疗的疗效，同时减少转移。涵盖领域：本综述讨论肿瘤血管正常化（TVN）作为抗血管生成癌症治疗的替代策略。我们总结了已开发出的使肿瘤血管正常化的（临床前）策略及其增强标准治疗的潜力。值得注意的是，我们描述了靶向内皮细胞代谢如何通过引发TVN为抗血管生成治疗提供新的可能性。专家观点：目前临床上有几种靶向VEGF信号传导的药物用于抗血管生成癌症治疗。然而，过度的血管修剪会阻碍灌注并导致肿瘤缺氧，已知这会促进癌细胞扩散并损害放疗、化疗和免疫治疗。正常化的血管可减轻肿瘤缺氧，阻碍癌细胞进入血管并增强抗癌治疗。新数据表明，靶向内皮细胞代谢是通过促进TVN进行抗血管生成癌症治疗的替代策略。
