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Inflammation and Altered Drug Clearance in Cancer: Transcriptional Repression of a Human CYP3A4 Transgene in Tumor‐bearing Mice
Author(s) -
Robertson GR,
Liddle C,
Clarke SJ
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2008.55
Subject(s) - cyp3a4 , psychological repression , inflammation , drug , transgene , clinical pharmacology , pharmacology , genetically modified mouse , cancer , biology , cancer research , medicine , immunology , gene , metabolism , gene expression , endocrinology , cytochrome p450 , genetics
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. Clinical Pharmacology & Therapeutics (2008); 83 , 6, 894–897 doi: 10.1038/clpt.2008.55