Anderson Joshua C, McFarland Braden C, Gladson Candece L
Department of Pathology, Division of Neuropathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Expert Rev Mol Med. 2008 Aug 7;10:e23. doi: 10.1017/S1462399408000768.
Antiangiogenesis approaches have the potential to be particularly effective in the treatment of glioblastoma tumours. These tumours exhibit extremely high levels of neovascularisation, which may contribute to their extremely aggressive behaviour, not only by providing oxygenation and nutrition, but also by establishing a leaky vasculature that lacks a blood-brain barrier. This leaky vasculature enables migration of tumour cells, as well as the build up of fluid, which exacerbates tissue damage due to increased intracranial pressure. Here, we discuss the considerable progress that has been made in the identification of the pro- and antiangiogenic factors produced by glioblastoma tumours and the effects of these molecules in animal models of the disease. The safety and efficacy of some of these approaches have now been demonstrated in clinical trials. However, the ability of tumours to overcome these therapies and to re-establish angiogenesis requires further clinical research regarding potential multimodality therapies, as well as basic research into the regulation of angiogenesis by as yet unidentified factors. Optimisation of noninvasive procedures for monitoring of angiogenesis would greatly facilitate such research.
抗血管生成方法在胶质母细胞瘤的治疗中可能具有特别显著的效果。这些肿瘤呈现出极高水平的新生血管形成,这不仅通过提供氧合作用和营养物质,还通过建立缺乏血脑屏障的渗漏血管系统,可能导致其极具侵袭性的行为。这种渗漏的血管系统使得肿瘤细胞能够迁移,同时也会导致液体堆积,由于颅内压升高而加剧组织损伤。在此,我们讨论了在胶质母细胞瘤产生的促血管生成因子和抗血管生成因子的鉴定方面所取得的重大进展,以及这些分子在该疾病动物模型中的作用。其中一些方法的安全性和有效性现已在临床试验中得到证实。然而,肿瘤克服这些治疗并重新建立血管生成的能力,需要进一步开展关于潜在多模态疗法的临床研究,以及对尚未明确的因子调控血管生成的基础研究。优化用于监测血管生成的非侵入性程序将极大地推动此类研究。