Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands (J.R.v.B., E.J.M.H., V.L.T., A.W.G.); and Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology, Lausanne, Switzerland (P.N.-S.).
Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands (J.R.v.B., E.J.M.H., V.L.T., A.W.G.); and Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology, Lausanne, Switzerland (P.N.-S.)
Pharmacol Rev. 2015;67(2):441-61. doi: 10.1124/pr.114.010215.
The concept of antiangiogenic therapy in cancer treatment has led to the approval of different agents, most of them targeting the well known vascular endothelial growth factor pathway. Despite promising results in preclinical studies, the efficacy of antiangiogenic therapy in the clinical setting remains limited. Recently, awareness has emerged on resistance to antiangiogenic therapies. It has become apparent that the intricate complex interplay between tumors and stromal cells, including endothelial cells and associated mural cells, allows for escape mechanisms to arise that counteract the effects of these targeted therapeutics. Here, we review and discuss known and novel mechanisms that contribute to resistance against antiangiogenic therapy and provide an outlook to possible improvements in therapeutic approaches.
癌症治疗中的抗血管生成治疗概念导致了不同药物的批准，其中大多数药物针对众所周知的血管内皮生长因子途径。尽管在临床前研究中取得了有希望的结果，但抗血管生成治疗在临床环境中的疗效仍然有限。最近，人们已经意识到对抗血管生成治疗的耐药性。显然，肿瘤与基质细胞（包括内皮细胞和相关的壁细胞）之间复杂的相互作用允许出现逃避机制，抵消这些靶向治疗的作用。在这里，我们回顾和讨论了导致抗血管生成治疗耐药的已知和新机制，并对治疗方法的可能改进提供了展望。
