VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside.
VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside.
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DOI：
10.18632/oncotarget.6918
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发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
de Vries EG
中科院分区：
文献类型：
--
作者：
Arjaans M;Schröder CP;Oosting SF;Dafni U;Kleibeuker JE;de Vries EG
血管内皮生长因子（VEGF）通路靶向药物已与其他抗癌药物联合使用，从而提高了对宫颈癌、胃癌、肺癌、结肠癌和直肠癌、卵巢癌和乳腺癌的疗效。VEGF通路靶向药物诱导的血管正常化影响肿瘤药物摄取。在贝伐单抗治疗后，临床前和临床研究显示放射性标记抗体和两种化疗药物的肿瘤递送减少。血管正常化过程中血管孔径的减小可能解释了肿瘤药物摄取的减少。此外，在结直肠癌患者中，将贝伐单抗添加到西妥昔单抗或帕尼单抗中，或在乳腺癌患者中添加到曲妥珠单抗中，并没有改善疗效。然而，贝伐单抗与化疗联合确实增加了某些癌症类型的疗效。选择可能从联合治疗中获益的患者的新型生物标志物，例如血管生成抑制剂对肿瘤灌注的影响，需要创新的试验设计和大型临床试验。放射性标记药物的小型成像研究可用于间期，以进一步了解VEGF靶向治疗、血管正常化和肿瘤药物递送之间的相互作用。
Vascular endothelial growth factor (VEGF) pathway targeting agents have been combined with other anticancer drugs, leading to improved efficacy in carcinoma of the cervix, stomach, lung, colon and rectum, ovary, and breast. Vessel normalization induced by VEGF pathway targeting agents influences tumor drug uptake. Following bevacizumab treatment, preclinical and clinical studies have shown a decrease in tumor delivery of radiolabeled antibodies and two chemotherapeutic drugs. The decrease in vessel pore size during vessel normalization might explain the decrease in tumor drug uptake. Moreover, the addition of bevacizumab to cetuximab, or panitumumab in colorectal cancer patients or to trastuzumab in breast cancer patients, did not improve efficacy. However, combining bevacizumab with chemotherapy did increase efficacy in some cancer types. Novel biomarkers to select patients who may benefit from combination therapies, such as the effect of an angiogenesis inhibitor on tumor perfusion, requires innovative trial designs and large clinical trials. Small imaging studies with radiolabeled drugs could be used in the interphase to gain further insight into the interplay between VEGF targeted therapy, vessel normalization and tumor drug delivery.
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