AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients
AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients
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DOI：
10.1016/j.ccr.2006.11.021
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发表时间：
2007-01-01
期刊：
影响因子：
50.3
通讯作者：
Jain, Rakesh K.
中科院分区：
文献类型：
--
作者：
Batchelor, Tracy T.;Sorensen, A. Gregory;Jain, Rakesh K.
使用 MRI 技术，我们在此表明，通过每天服用 AZD2171（一种口服 VEGF 受体酪氨酸激酶抑制剂），复发性胶质母细胞瘤患者的肿瘤血管正常化起效快，时间长，但可逆，并且具有减轻水肿的显着临床益处。正常化的逆转在 28 天后开始，尽管某些特征持续了长达四个月。当肿瘤逃避治疗时，碱性 FGF、SDF1 α 和活循环内皮细胞 (CEC) 会增加，而当肿瘤在药物中断后进展时，循环祖细胞 (CPC) 会增加。我们的研究深入了解了此类药物在复发性胶质母细胞瘤患者中的不同作用机制，并表明联合治疗的时机可能对于优化针对该肿瘤的活性至关重要。
Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1 alpha, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.