Inhibition of angiogenesis and the angiogenesis/invasion shift
Inhibition of angiogenesis and the angiogenesis/invasion shift
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DOI：
10.1042/bst20110710
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发表时间：
2011-12-01
影响因子：
3.9
通讯作者：
Hagedorn, Martin
中科院分区：
文献类型：
--
作者：
Bikfalvi, Andreas;Moenner, Michel;Hagedorn, Martin
血管生成已成为癌症治疗的主要靶点。然而，目前的治疗策略有其局限性，并提出了一些问题。在大多数肿瘤中，与单独的常规化疗相比，靶向VEGF（血管内皮生长因子）的抗血管生成治疗仅具有有限的总体生存获益，并且揭示了几种特定形式的抗VEGF治疗耐药性。越来越多的证据表明，抗vegf治疗可能通过选择高侵袭性肿瘤细胞或耐缺氧细胞，或通过上调血管生成替代途径（如成纤维细胞生长因子）或触发新侵袭程序的基因来诱导肿瘤细胞侵袭。我们已经确定了新的基因上调在胶质瘤生长的小鸡CAM（绒毛膜尿囊膜）。我们的研究结果表明，在实验性胶质瘤模型中，抗血管生成治疗可驱动与胶质瘤患者疾病侵袭性相关的关键基因的表达。我们已经确定了肿瘤细胞中的一种分子机制，允许从血管生成到侵入程序的转换。此外，我们正专注于研究部分独立于VEGF的替代抑制剂。这些内源性分子在控制肿瘤生长中发挥作用，可能构成进一步开发新的治疗或诊断工具的起点。
Angiogenesis has become a major target in cancer therapy. However, current therapeutic strategies have their limitations and raise several problems. In most tumours, anti-angiogenesis treatment targeting VEGF (vascular endothelial growth factor) has only limited overall survival benefit compared with conventional chemotherapy alone, and reveals several specific forms of resistance to anti-VEGF treatment. There is growing evidence that anti-VEGF treatment may induce tumour cell invasion by selecting highly invasive tumour cells or hypoxia-resistant cells, or by up-regulating angiogenic alternative pathways such as FGFs (fibroblast growth factors) or genes triggering new invasive programmes. We have identified new genes up-regulated during glioma growth on the chick CAM (chorioallantoic membrane). Our results indicate that anti-angiogenesis treatment in the experimental glioma model drives expression of critical genes which relate to disease aggressiveness in glioblastoma patients. We have identified a molecular mechanism in tumour cells that allows the switch from an angiogenic to invasive programme. Furthermore, we are focusing our research on alternative inhibitors that act, in part, independently of VEGF. These are endogenous molecules that play a role in the control of tumour growth and may constitute a starting point for further development of novel therapeutic or diagnostic tools.