ZD1839 ('Iressa'), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model

被引:155
作者
Williams, KJ [1 ]
Telfer, BA
Stratford, IJ
Wedge, SR
机构
[1] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PL, Lancs, England
[2] AstraZeneca, Canc & Infect Biosci, Macclesfield SK10 4TG, Cheshire, England
基金
英国医学研究理事会;
关键词
ZD; 1839; EGFR-TKI; radiotherapy; LoVo xenograft; Iressa;
D O I
10.1038/sj/bjc/6600182
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The effect of ZD 1839 ('Iressa'), a specific inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor, on the radiation response of human tumour cells (LoVo colorectal carcinoma) was evaluated in vitro and in vivo. ZD 1839 (0.5 mum, incubated days 1 - 5) significantly increased the anti-proliferative effect of fractionated radiation treatment (2 Gy day(-1), days 1 - 3) on LoVo cells grown in vitro (P=0.002). ZD 1839 combined with either single or fractionated radiotherapy in mice bearing LoVo tumour xenografts, also produced a highly significant increase in tumour growth inhibition (P less than or equal to 0.001) when compared to treatment with either modality alone. The radio-potentiating effect of ZD1839 was more apparent when radiation was administered in a fractionated protocol. This phenomenon may be attributed to an anti proliferative effect of ZD1839 on tumour cell re-population between radiotherapy fractions. These data suggest radiotherapy with adjuvant ZD l 839 could enhance treatment response. Clinical investigation of ZD 1839 in combination with radiotherapy is therefore warranted. (C) 2002 Cancer Research UK.
引用
收藏
页码:1157 / 1161
页数:5
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