VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside

被引:94
作者
Arjaans, Marlous [1 ]
Schroder, Carolina P. [1 ]
Oosting, Sjoukje F. [1 ]
Dafni, Urania [2 ]
Kleibeuker, Josee E. [3 ]
de Vries, Elisabeth G. E. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands
[2] Univ Athens, Lab Biostat, Athens, Greece
[3] Univ Cambridge, Dept Mat Sci & Met, Pembroke St, Cambridge CB2 3QZ, England
关键词
antiangiogenic drugs; blood vessel normalization; tumor drug delivery; METASTATIC COLORECTAL-CANCER; PHASE-III TRIAL; DOUBLE-BLIND; ANTIANGIOGENIC THERAPY; 1ST-LINE TREATMENT; BREAST-CANCER; GROWTH-FACTOR; VASCULAR NORMALIZATION; BLOOD-VESSELS; ANTI-VEGF;
D O I
10.18632/oncotarget.6918
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:21247 / 21258
页数:12
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