ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Contribution of ABCC4-mediated gastric transport to the absorption and efficacy of dasatinib.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Methotrexate Decreases Tenofovir Exposure in Antiretroviral-Suppressed Individuals Living With HIV.Journal of acquired immune deficiency syndromes (1999) · 2020Trial
- Does a glass of Coke boost the exposure to imatinib in gastrointestinal stromal tumour patients after gastrectomy?British journal of clinical pharmacology · 2017Trial
- Fast-Dissolving and Highly Soluble Dasatinib Multicomponent Crystals Efficiently Inhibit Leukemia Cell Viability.ACS omega · 2026Article
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Drug-drug interactions in targeted cancer therapies: a focus on tyrosine kinase inhibitors.Expert review of clinical pharmacology · 2025Review
- ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Cellular Uptake and Transport Mechanism of 6-Mercaptopurine Nanomedicines for Enhanced Oral Bioavailability.International journal of nanomedicine · 2023Article
- Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers.Cancers · 2022Review
- Transport and metabolism of tyrosine kinase inhibitors associated with chronic myeloid leukemia therapy: a review.Molecular and cellular biochemistry · 2022Review
- Article
- Interactions of anti-COVID-19 drug candidates with hepatic transporters may cause liver toxicity and affect pharmacokinetics.Scientific reports · 2021Article
- Generation of Knockout and Transgenic Zebrafish to Characterize Abcc4 Functions in Detoxification and Efflux of Lead.International journal of molecular sciences · 2021Article
- Vitamin D levels do not cause vitamin-drug interactions with dexamethasone or dasatinib in mice.PloS one · 2021Article
- Influence of YES1 Kinase and Tyrosine Phosphorylation on the Activity of OCT1.Frontiers in pharmacology · 2021Article
- Study on mechanism of elemene reversing tumor multidrug resistance based on luminescence pharmacokinetics in tumor cellsRSC advances · 2020Article
- Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma.Cancers · 2020Review
- Pharmacology of tyrosine kinase inhibitors in chronic myeloid leukemia; a clinician's perspective.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2020Review
- The effect of gastrectomy on regorafenib exposure and progression-free survival in patients with advanced gastrointestinal stromal tumours.British journal of clinical pharmacology · 2019Article
- Differential effects of thiopurine methyltransferase (TPMT) and multidrug resistance-associated protein gene 4 (MRP4) on mercaptopurine toxicity.Cancer chemotherapy and pharmacology · 2017Article
- A phosphotyrosine switch regulates organic cation transporters.Nature communications · 2016Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeSeveral oral multikinase inhibitors are known to interact in vitro with the human ATP-binding cassette transporter ABCC4 (MRP4), but the in vivo relevance of this interaction remains poorly understood. We hypothesized that host ABCC4 activity may influence the pharmacokinetic profile of dasatinib and subsequently affect its antitumor properties. EXPERIMENTAL
designTransport of dasatinib was studied in cells transfected with human ABCC4 or the ortholog mouse transporter, Abcc4. Pharmacokinetic studies were done in wild-type and Abcc4-null mice. The influence of Abcc4 deficiency on dasatinib efficacy was evaluated in a model of Ph(+) acute lymphoblastic leukemia by injection of luciferase-positive, p185(BCR-ABL)-expressing Arf(-/-) pre-B cells.
resultsDasatinib accumulation was significantly changed in cells overexpressing ABCC4 or Abcc4 compared with control cells (P < 0.001). Deficiency of Abcc4 in vivo was associated with a 1.75-fold decrease in systemic exposure to oral dasatinib, but had no influence on the pharmacokinetics of intravenous dasatinib. Abcc4 was found to be highly expressed in the stomach, and dasatinib efflux from isolated mouse stomachs ex vivo was impaired by Abcc4 deficiency (P < 0.01), without any detectable changes in gastric pH. Abcc4-null mice receiving dasatinib had an increase in leukemic burden, based on bioluminescence imaging, and decreased overall survival compared with wild-type mice (P = 0.048).
conclusionsThis study suggests that Abcc4 in the stomach facilitates the oral absorption of dasatinib, and it possibly plays a similar role for other orally administered substrates, such as acetylsalicylic acid. This phenomenon also provides a mechanistic explanation for the malabsorption of certain drugs following gastric resection.
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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.