ArticleInternational journal of pharmaceutics2012
Co-administration strategy to enhance brain accumulation of vandetanib by modulating P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp1/Abcg2) mediated efflux with m-TOR inhibitors.
Article in International journal of pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 80 citations in OpenAlex.
- A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
- CNS distribution and preclinical activity of the PI3K/AKT inhibitors inavolisib and ipatasertib in pediatric-type diffuse high-grade gliomas.Cancer chemotherapy and pharmacology · 2026Article
- Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Review
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- Review
- Everolimus in pituitary tumor: a review of preclinical and clinical evidence.Frontiers in endocrinology · 2024Review
- Therapeutic avenues for targeting treatment challenges of diffuse midline gliomas.Neoplasia (New York, N.Y.) · 2023Review
- RET aberrant cancers and RET inhibitor therapies: Current state-of-the-art and future perspectives.Pharmacology & therapeutics · 2023Review
- The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells.Science signaling · 2022Article
- Therapeutic strategies of glioblastoma (GBM): The current advances in the molecular targets and bioactive small molecule compounds.Acta pharmaceutica Sinica. B · 2022Review
- Repurposing Vandetanib plus Everolimus for the Treatment ofCancer discovery · 2022Article
- Real-world pharmacokinetics and pharmacodynamics of everolimus in metastatic breast cancer.Investigational new drugs · 2021Article
- Everolimus improves the efficacy of dasatinib in PDGFRα-driven glioma.The Journal of clinical investigation · 2020Article
- A comprehensive review in improving delivery of small-molecule chemotherapeutic agents overcoming the blood-brain/brain tumor barriers for glioblastoma treatment.Drug delivery · 2019Review
- Brain Distribution of a Panel of Epidermal Growth Factor Receptor Inhibitors Using Cassette Dosing in Wild-Type andDrug metabolism and disposition: the biological fate of chemicals · 2019Article
- Autophagic and Apoptotic Pathways as Targets for Chemotherapy in Glioblastoma.International journal of molecular sciences · 2018Review
- Clinical development of RET inhibitors in RET-rearranged non-small cell lung cancer: Update.Oncology reviews · 2018Article
- Development of the CNS TAP tool for the selection of precision medicine therapies in neuro-oncology.Journal of neuro-oncology · 2018Article
- Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data.Neuro-oncology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The objectives of this study were (i) to characterize the interaction of vandetanib with P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp1) in vitro and in vivo (ii) to study the modulation of P-gp and BCRP mediated efflux of vandetanib with specific transport inhibitors and m-TOR inhibitors, everolimus and temsirolimus. Cellular accumulation and bi-directional transport studies in MDCKII cell monolayers were conducted to delineate the role of efflux transporters on disposition of vandetanib. Brain distribution studies were conducted in male FVB wild-type mice with vandetanib administered intravenously either alone or in the presence of specific inhibitors and m-TOR inhibitors. In vitro studies suggested that vandetanib is a high affinity substrate of Bcrp1 but is not transported by P-gp. Interestingly, in vivo brain distribution studies in FVB wild type mice indicated that vandetanib penetration into the brain is restricted by both Bcrp1 and P-gp mediated active efflux at the blood brain barrier (BBB). Co-administration of elacridar, a dual P-gp/BCRP inhibitor increased the brain to plasma concentration ratio of vandetanib upto 5 fold. Of the two m-TOR pathway inhibitors examined; everolimus showed potent effect on modulating vandetanib brain penetration whereas no significant affect on vandetanib brain uptake was observed following temsirolimus co-administration. This finding could be clinically relevant as everolimus can provide synergistic pharmacological effect in addition to primary role of vandetanib efflux modulation at BBB for the treatment of brain tumors.
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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.