ArticlePharmaceutical research2013
Extra-hepatic cancer represses hepatic drug metabolism via interleukin (IL)-6 signalling.
Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Pharmacokinetics of seven major components in AβJournal of natural medicines · 2025Article
- Disease-drug and drug-drug interaction in COVID-19: Risk and assessment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Candidate Glycoprotein Biomarkers for Canine Visceral Hemangiosarcoma and Validation Using Semi-Quantitative Lectin/Immunohistochemical Assays.Veterinary sciences · 2021Article
- Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.Pharmacology & therapeutics · 2020Review
- Cytochrome P450-mediated drug interactions in COVID-19 patients: Current findings and possible mechanisms.Medical hypotheses · 2020Article
- Altered cytochrome 2E1 and 3A P450-dependent drug metabolism in advanced ovarian cancer correlates to tumour-associated inflammation.British journal of pharmacology · 2019Article
- Pharmacokinetics, pharmacodynamics and pharmacogenetics associated with nonsteroidal anti-inflammatory drugs and opioids in pediatric cancer patients.Expert opinion on drug metabolism & toxicology · 2017Review
- Integrin Receptors Play a Key Role in the Regulation of Hepatic CYP3A.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Color Doppler ultrasound and gamma imaging of intratumorally injected 500 nm iron-silica nanoshells.ACS nano · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIn many cancer patients, the malignancy causes reduced hepatic drug clearance leading to potentially serious complications from the use of anticancer drugs. The mechanisms underlying this phenomenon are poorly understood. We aimed to identify tumor-associated inflammatory pathways that alter drug response and enhance chemotherapy-associated toxicity.
methodsWe studied inflammatory pathways involved in extra-hepatic tumor mediated repression of CYP3A, a major hepatic drug metabolizing cytochrome P450 subfamily, using a murine Engelbreth-Holm-Swarm sarcoma model. Studies in IL-6 knockout mice determined the source of elevated IL-6 in tumor-bearing animals and monoclonal antibodies against IL-6 were used to intervene in this inflammatory pathway.
resultsOur studies confirm elevated plasma IL-6 levels and reveal activation of Jak/Stat and Mapk signalling pathways and acute phase proteins in livers of tumor-bearing mice. Circulating IL-6 was predominantly produced by the tumor xenograft, rather than being host derived. Anti IL-6 antibody intervention partially reversed tumor-mediated inflammation and Cyp3a gene repression.
conclusionsIL-6 is an important player in cancer-related repression of CYP3A-mediated drug metabolism and activation of the acute phase response. Targeting IL-6 in cancer patients may prove an effective approach to alleviating cancer-related phenomena, such as adverse drug-related outcomes commonly associated with cancer chemotherapy.
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