ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Extrahepatic cancer suppresses nuclear receptor-regulated drug metabolism.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- Systemic Mobilization of Breast Cancer Resistance Protein in Response to Oncogenic Stress.Cancers · 2022Article
- Disrupted hepatic pentose phosphate pathway directly participates in and indirectly promotes CYP3A reduction: A new strategy for CYP3A-mediated drug hepatotoxicity.British journal of pharmacology · 2020Article
- Intrinsic and Extrinsic Pharmacokinetic Variability of Small Molecule Targeted Cancer Therapy.Clinical and translational science · 2020Article
- Altered cytochrome 2E1 and 3A P450-dependent drug metabolism in advanced ovarian cancer correlates to tumour-associated inflammation.British journal of pharmacology · 2019Article
- Reduced Clearance of Phenobarbital in Advanced Cancer Patients near the End of Life.European journal of drug metabolism and pharmacokinetics · 2019Article
- Prognostic Nutritional Index as an independent prognostic factor in locoregionally advanced squamous cell head and neck cancer.ESMO open · 2018Article
- Reduction of p53 by knockdown of theCellular and molecular gastroenterology and hepatology · 2016Article
- Pan-cancer analyses of the nuclear receptor superfamily.Nuclear receptor research · 2015Article
- Cooperative behavior of the nuclear receptor superfamily and its deregulation in prostate cancer.Carcinogenesis · 2014Article
- Intestinal glucuronidation protects against chemotherapy-induced toxicity by irinotecan (CPT-11).Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Extra-hepatic cancer represses hepatic drug metabolism via interleukin (IL)-6 signalling.Pharmaceutical research · 2013Article
- Color Doppler ultrasound and gamma imaging of intratumorally injected 500 nm iron-silica nanoshells.ACS nano · 2013Article
- Drug disposition in pathophysiological conditions.Current drug metabolism · 2012Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeTo determine the mechanisms by which tumors situated in extrahepatic sites can cause profound changes in hepatic drug clearance, contributing to altered drug response and chemotherapy resistance. EXPERIMENTAL
designWe studied in wild-type or transgenic CYP3A4 reporter mice implanted with the murine Engelbreth-Holm-Swarm sarcoma changes in nuclear receptor and hepatic transcription factor expression and/or function, particularly related to CYP3A gene regulation.
resultsRepression of hepatic CYP3A induction was dramatic and associated with reduced levels of C/EBPβ isoforms, impaired pregnane X receptor, and constitutive androstane receptor function. Unexpectedly, extrahepatic tumors strongly reduced nuclear accumulation of retinoid X receptor alpha (RXRα) in hepatocytes, providing a potential explanation for impaired function of nuclear receptors that rely on RXRα dimerization. Profiling revealed 38 nuclear receptors were expressed in liver with 14 showing between 1.5- and four-fold reduction in expression in livers of tumor-bearing animals, including Car, Trβ, Lxrβ, Pparα, Errα/β, Reverbα/β, and Shp. Altered Pparα and γ induction of target genes provided additional evidence of perturbed hepatic metabolic control elicited by extrahepatic tumors.
conclusionsExtrahepatic malignancy can affect hepatic drug metabolism by nuclear receptor relocalization and decreased receptor expression and function. These findings could aid the design of intervention strategies to normalize drug clearance and metabolic pathways in cancer patients at risk of chemotherapy-induced toxicity or cancer cachexia.
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