University Bordeaux, LAMC, UMR 1029, F-3400 Talence, France.
Biochem Soc Trans. 2011 Dec;39(6):1560-4. doi: 10.1042/BST20110710.
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.
血管生成已成为癌症治疗的主要靶点。然而，目前的治疗策略存在局限性，并引发了一些问题。与单独使用传统化疗相比，针对血管内皮生长因子（VEGF）的抗血管生成治疗在大多数肿瘤中仅具有有限的总体生存获益，并且表现出几种针对抗 VEGF 治疗的特定形式的耐药性。越来越多的证据表明，抗 VEGF 治疗可能通过选择高度侵袭性的肿瘤细胞或缺氧耐受细胞，或通过上调成纤维细胞生长因子（FGFs）等血管生成替代途径或触发新侵袭程序的基因，诱导肿瘤细胞侵袭。我们已经鉴定出在鸡胚尿囊膜（CAM）上生长的神经胶质瘤中上调的新基因。我们的结果表明，实验性神经胶质瘤模型中的抗血管生成治疗驱动与胶质母细胞瘤患者疾病侵袭性相关的关键基因的表达。我们已经在肿瘤细胞中确定了一种分子机制，该机制允许从血管生成到侵袭程序的转变。此外，我们的研究重点是部分独立于 VEGF 起作用的替代抑制剂。这些是内源性分子，在肿瘤生长的控制中发挥作用，可能成为开发新型治疗或诊断工具的起点。
