Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Crit Rev Oncol Hematol. 2014 Oct;92(1):38-48. doi: 10.1016/j.critrevonc.2014.05.001. Epub 2014 May 10.
Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which generate a network of disorganized, tortuous and permeable vessels. Recruitment of bone marrow derived cells (BMDC) is crucial for vasculogenesis. These cells may act as vascular progenitors by integrating into the newly formed blood vessels or as vascular modulators by releasing pro-angiogenic factors. In patients with recurrent GBM, anti-vascular endothelial growth factor (VEGF) therapy has been evaluated in combination with chemotherapy, yielding improvements in progression-free survival (PFS). However, benefits are temporary as vascular tumors acquire angiogenic pathways independently of VEGF. Specifically, acute hypoxia following prolonged VEGF depletion induces the recruitment of certain myeloid cell subpopulations, which highly contribute to treatment refractoriness. Here we review the molecular mechanisms of neovascularization in relation to bevacizumab therapy with special emphasis on the recruitment of BMDCs and possible combination therapies for GBM patients.
胶质母细胞瘤（GBM）是一种高度血管化的肿瘤，其特征是肿瘤生长迅速且具有侵袭性，随后出现缺氧、低氧和新生血管生成，从而产生了一个紊乱、扭曲和通透性的血管网络。骨髓来源细胞（BMDC）的募集对于血管生成至关重要。这些细胞可以通过整合到新形成的血管中作为血管祖细胞，或者通过释放促血管生成因子作为血管调节剂。在复发性 GBM 患者中，抗血管内皮生长因子（VEGF）治疗已与化疗联合进行了评估，从而改善了无进展生存期（PFS）。然而，这些益处是暂时的，因为血管肿瘤会独立于 VEGF 获得血管生成途径。具体而言，在 VEGF 耗竭后长时间出现的急性缺氧会诱导某些髓样细胞亚群的募集，这些细胞群高度促成了治疗抵抗。本文综述了与贝伐珠单抗治疗相关的新生血管形成的分子机制，特别强调了 BMDC 的募集以及 GBM 患者的可能联合治疗策略。
