Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan
Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan
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DOI：
10.1111/j.1600-0463.2010.02631.x
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发表时间：
2010-08-01
期刊：
影响因子：
2.8
通讯作者：
Lassen, Ulrik
中科院分区：
文献类型：
--
作者：
Hasselbalch, Benedikte;Eriksen, Jesper Grau;Lassen, Ulrik
最近的几项研究表明，使用血管内皮生长因子中和抗体贝伐珠单抗进行抗血管生成治疗对复发性高级别胶质瘤具有有益作用。在当前的研究中，对涉及血管生成、缺氧和表皮生长因子受体（EGFR）途径介质的生物标志物进行了免疫组织化学评估。肿瘤组织取自之前的一项 II 期研究，该研究使用 EGFR 抑制剂西妥昔单抗联合贝伐单抗和伊立替康治疗复发性原发性多形性胶质母细胞瘤 (GBM) 患者。在 37 名具有可用肿瘤组织的患者中，29 名可评估疗效。我们同时对 21 名接受贝伐珠单抗和伊立替康治疗的 GBM 患者的肿瘤组织进行了免疫组织化学染色。我们发现缺氧相关标记之间存在相关趋势，表明它们具有相同的调节机制。 EGFR 相关生物标志物均未显示出彼此之间任何显着相关性。单独或组合测试的生物标志物均无法识别可能从贝伐单抗和伊立替康（添加或不添加西妥昔单抗）中受益的患者群体。仍然迫切需要一种或多种能够预测抗血管生成治疗功效的可靠且可重复的生物标志物。
Several recent studies have demonstrated a beneficial effect of anti-angiogenic treatment with the vascular endothelial growth factor-neutralizing antibody bevacizumab in recurrent high-grade glioma. In the current study, immunohistochemical evaluation of biomarkers involved in angiogenesis, hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan. Of the 37 patients with available tumor tissue, 29 were evaluable for response. We concurrently performed immunohistochemical stainings on tumor tissue from 21 GBM patients treated with bevacizumab and irinotecan. We found a tendency of correlation between the hypoxia-related markers, indicating that they share the same regulatory mechanisms. None of the EGFR-related biomarkers showed any significant correlations with each other. None of the biomarkers tested alone or in combination could identify a patient population likely to benefit from bevacizumab and irinotecan, with or without the addition of cetuximab. There is still an urgent need for one or more reliable and reproducible biomarkers able to predict the efficacy of anti-angiogenic therapy.