Inflammation and altered drug clearance in cancer: Transcriptional repression of a human CYP3A4 transgene in tumor-bearing mice

被引：38

作者：

Robertson, G. R. ^{[1
]}

Liddle, C. ^{[2
]}

Clarke, S. J. ^{[1
]}

机构：

[1] Univ Sydney, Concord RG Hosp, ANZAC Res Inst, Canc Pharmacol Unit, Concord, NSW, Australia

[2] Univ Sydney, Westmead Millennium Inst, Storr Liver Unit, Westmead, NSW 2145, Australia

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2008年 / 83卷 / 06期

关键词：

D O I：

10.1038/clpt.2008.55

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A tumor-associated inflammatory response has recently been found to contribute to the considerable interindividual variability in cytotoxic drug clearance seen in cancer patients. Circulating inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), correlate with excessive drug toxicity caused by reduced CYP3A4-mediated metabolism. This article outlines the use of a transgenic mouse model of human CYP3A4 regulation to demonstrate that extrahepatic tumors elicit an inflammatory response, leading to transcriptional repression of the CYP3A4 gene as well as of other drug clearance pathways.

引用

页码：894 / 897

页数：4

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