Zd6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy

被引:26
作者
Frederick, B
Gustafson, D
Bianco, C
Ciardiello, F
Dimery, I
Raben, D
机构
[1] Univ Colorado, Hlth Sci Ctr, Dept Radiat Oncol, Aurora, CO 80010 USA
[2] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO 80010 USA
[3] Univ Pisa, Dipartimento Oncol Trapianti & Nuove Technol Med, Pisa, Italy
[4] Univ Naples Federico II, Dept Mol & Clin Endocrinol, Naples, Italy
[5] AstraZeneca, Wilmington, DE USA
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2006年 / 64卷 / 01期
关键词
tyrosine kinase inhibitor; vascular endothelial growth factor receptor; radiotherapy; angiogenesis;
D O I
10.1016/j.ijrobp.2005.05.050
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Radiation enhances both epithelial growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression, which are a part of key pathways for tumor progression. Some tumors may not respond well to EGFR inhibitors alone or may develop resistance to EGFR inhibitors. Therefore, drug therapy targeted to VEGF receptors and EGFRs, when combined with radiotherapy (RT), may improve tumor control and provide wider applicability. This article focuses on ZD6474, an inhibitor of EGFR and VEGF receptor signaling in combination with RT. We discuss preclinical and clinical studies with RT and inhibitors of VEGF or EGFR signaling first. We then address issues associated with ZD6474 pharmacokinetic dosing, and scheduling when combined with RT. We also discuss ZD6474 in the context of anti-EGFR therapy resistance. Dual inhibition of EGFR and VEGF receptor signaling pathways shows promise in enhancing RT efficacy. (c) 2006 Elsevier Inc.
引用
收藏
页码:33 / 37
页数:5
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