Cancer Genomics Centre Netherlands and Centre for BioMedical Genetics, Department of Molecular Cell Biology, Leiden University Medical Center, Building-2, S1-P, PO-box 9600, 2300 RC Leiden, The Netherlands.
Expert Opin Ther Targets. 2013 Apr;17(4):421-35. doi: 10.1517/14728222.2013.758716. Epub 2013 Jan 17.
Although cancer treatment has evolved substantially in the past decades, cancer-related mortality rates are still increasing. Therapies targeting tumor angiogenesis, crucial for the growth of solid tumors, mainly target vascular endothelial growth factor (VEGF) and have been clinically applied during the last decade. However, these therapies have not met high expectations, which were based on therapeutic efficacy in animal models. This can partly be explained by the upregulation of alternative angiogenic pathways. Therefore, additional therapies targeting other pro-angiogenic pathways are needed.
The transforming growth factor (TGF)-β signaling pathway plays an important role in (tumor) angiogenesis. Therefore, components of this pathway are interesting candidates for anti-angiogenic therapy. Endoglin, a co-receptor for various TGF-β family members, is specifically overexpressed in tumor vessels and endoglin expression is associated with metastasis and patient survival. Therefore, endoglin might be a good candidate for anti-angiogenic therapy. In this review, we discuss the potential of using endoglin to target the tumor vasculature for imaging and therapeutic purposes.
Considering the promising results from various in vitro studies, in vivo animal models and the first clinical trial targeting endoglin, we are convinced that endoglin is a valuable tool for the diagnosis, visualization and ultimately treatment of solid cancers.
尽管过去几十年癌症治疗有了很大的发展，但癌症相关的死亡率仍在上升。针对肿瘤血管生成的治疗方法，对实体瘤的生长至关重要，主要针对血管内皮生长因子（VEGF），并在过去十年中得到了临床应用。然而，这些治疗方法并没有达到很高的期望，这部分是基于动物模型中的治疗效果。这在一定程度上可以解释为替代血管生成途径的上调。因此，需要额外的针对其他促血管生成途径的治疗方法。
转化生长因子（TGF）-β信号通路在（肿瘤）血管生成中起着重要作用。因此，该途径的成分是抗血管生成治疗的有趣候选物。内格林（Endoglin）是各种 TGF-β家族成员的共受体，在肿瘤血管中特异性过表达，并且内格林的表达与转移和患者的生存有关。因此，内格林可能是抗血管生成治疗的一个很好的候选物。在这篇综述中，我们讨论了利用内格林靶向肿瘤血管进行成像和治疗的潜力。
考虑到来自各种体外研究、体内动物模型和第一个针对内格林的临床试验的有希望的结果，我们相信内格林是诊断、可视化和最终治疗实体癌的有价值的工具。
