ArticleCancer research2015
Hepatocellular Shuttling and Recirculation of Sorafenib-Glucuronide Is Dependent on Abcc2, Abcc3, and Oatp1a/1b.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- Influence of OATP1B1 Function on the Disposition of Sorafenib-β-D-Glucuronide.Clinical and translational science · 2017Trial
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Harnessing the microbiome: unveiling the influence of the gut microbiota on hepatobiliary cancer therapeutic strategies.Clinical and molecular hepatology · 2026Review
- Decoding Drug Interactions: Character and Degree of Pharmacokinetic Interactions Between Telmisartan and Sorafenib or Donafenib in Rats.Drug design, development and therapy · 2025Article
- Article
- The role of gut microbial β-glucuronidases in carcinogenesis and cancer treatment: a scoping review.Journal of cancer research and clinical oncology · 2024Article
- Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.Acta pharmaceutica Sinica. B · 2024Article
- Development and validation of a UPLC-MS/MS method for simultaneous detection of doxorubicin and sorafenib in plasma: Application to pharmacokinetic studies in rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Pharmacomicrobiomics in Anticancer Therapies: Why the Gut Microbiota Should Be Pointed Out.Genes · 2022Review
- Pharmacokinetic Interactions between Canagliflozin and Sorafenib or Lenvatinib in Rats.Molecules (Basel, Switzerland) · 2022Article
- Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers.Cancers · 2022Review
- Preclinical and Pilot Study of Type I FLT3 Tyrosine Kinase Inhibitor, Crenolanib, with Sorafenib in Acute Myeloid Leukemia and FLT3-Internal Tandem Duplication.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Boosting the oral bioavailability of anticancer drugs through intentional drug-drug interactions.Basic & clinical pharmacology & toxicology · 2022Review
- Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats.Pharmaceutics · 2021Article
- Article
- The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates.Frontiers in pharmacology · 2021Review
- The implications of ABCC3 in cancer drug resistance: can we use it as a therapeutic target?American journal of cancer research · 2021Review
- Influence of Probenecid on the Pharmacokinetics and Pharmacodynamics of Sorafenib.Pharmaceutics · 2020Article
- Review
- OATP1A/1B, CYP3A, ABCB1, and ABCG2 limit oral availability of the NTRK inhibitor larotrectinib, while ABCB1 and ABCG2 also restrict its brain accumulation.British journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Recently, an efficient liver detoxification process dubbed "hepatocyte hopping" was proposed on the basis of findings with the endogenous compound, bilirubin glucuronide. According to this model, hepatocytic bilirubin glucuronide can follow a liver-to-blood shuttling loop via Abcc3 transporter-mediated efflux and subsequent Oatp1a/1b-mediated liver uptake. We hypothesized that glucuronide conjugates of xenobiotics, such as the anticancer drug sorafenib, can also undergo hepatocyte hopping. Using transporter-deficient mouse models, we show here that sorafenib-glucuronide can be extruded from hepatocytes into the bile by Abcc2 or back into the systemic circulation by Abcc3, and that it can be taken up efficiently again into neighboring hepatocytes by Oatp1a/1b. We further demonstrate that sorafenib-glucuronide excreted into the gut lumen can be cleaved by microbial enzymes to sorafenib, which is then reabsorbed, supporting its persistence in the systemic circulation. Our results suggest broad relevance of a hepatocyte shuttling process known as "hepatocyte hopping"-a novel concept in clinical pharmacology-for detoxification of targeted cancer drugs that undergo hepatic glucuronidation, such as sorafenib.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.