ArticleCancer research2010
Tyrosine kinase inhibitor gefitinib enhances topotecan penetration of gliomas.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 71 citations in OpenAlex.
- 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
- Micro pharmacokinetics-pharmacodynamics monitoring of anti-Parkinson's disease drugs using a microphysiological BBB-brain organ-on-a-chip.Microsystems & nanoengineering · 2026Article
- Study on the Effect of Pharmaceutical Excipient PEG400 on the Pharmacokinetics of Baicalin in Cells Based on MRP2, MRP3, and BCRP Efflux Transporters.Pharmaceutics · 2024Article
- Modulation of the Blood-Brain Barrier for Drug Delivery to Brain.Pharmaceutics · 2021Review
- Pharmacokinetic Principles and Their Application to Central Nervous System Tumors.Pharmaceutics · 2020Review
- CNS penetration and pharmacodynamics of the CHK1 inhibitor prexasertib in a mouse Group 3 medulloblastoma model.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2020Article
- Effects of Pazopanib Monotherapy vs. Pazopanib and Topotecan Combination on Anaplastic Thyroid Cancer Cells.Frontiers in oncology · 2019Article
- Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway.Cancer management and research · 2018Article
- Targeted drug distribution in tumor extracellular fluid of GD2-expressing neuroblastoma patient-derived xenografts using SN-38-loaded nanoparticles conjugated to the monoclonal antibody 3F8.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived Xenografts.Pharmaceutical research · 2015Article
- Observational Evaluations of Mice during Cerebral Microdialysis for Pediatric Brain Tumor Research.Journal of the American Association for Laboratory Animal Science : JAALAS · 2015Article
- Preclinical examination of clofarabine in pediatric ependymoma: intratumoral concentrations insufficient to warrant further study.Cancer chemotherapy and pharmacology · 2015Article
- Phase I dosage finding and pharmacokinetic study of intravenous topotecan and oral erlotinib in adults with refractory solid tumors.Cancer chemotherapy and pharmacology · 2014Article
- Temozolomide down-regulates P-glycoprotein in human blood-brain barrier cells by disrupting Wnt3 signaling.Cellular and molecular life sciences : CMLS · 2014Article
- Induction of the unfolded protein response drives enhanced metabolism and chemoresistance in glioma cells.PloS one · 2013Article
- Screening candidate anticancer drugs for brain tumor chemotherapy: pharmacokinetic-driven approach for a series of (E)-N-(substituted aryl)-3-(substituted phenyl)propenamide analogues.Investigational new drugs · 2012Article
- Active efflux of Dasatinib from the brain limits efficacy against murine glioblastoma: broad implications for the clinical use of molecularly targeted agents.Molecular cancer therapeutics · 2012Article
- Progesterone receptor downregulates breast cancer resistance protein expression via binding to the progesterone response element in breast cancer.Cancer science · 2012Article
- Article
- Paclitaxel- and lapatinib-loaded lipopolymer micelles overcome multidrug resistance in prostate cancer.Drug delivery and translational research · 2011Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, increases brain parenchymal extracellular fluid (ECF) accumulation of topotecan, a substrate of the ATP-binding cassette (ABC) transporters P-glycoprotein (Pgp/MDR-1) and breast cancer resistance protein (BCRP/ABCG2). The effect of modulating these transporters on topotecan penetration in gliomas has not been thoroughly studied. Thus, we performed intracerebral microdialysis on mice bearing orthotopic human gliomas (U87 and MT330) and assessed topotecan tumor ECF (tECF) penetration and the effect of gefitinib on topotecan tECF penetration and intratumor topotecan distribution. We found that topotecan penetration (P(tumor)) of U87 was 0.96 +/- 0.25 (n = 7) compared with that of contralateral brain (P(contralateral), 0.42 +/- 0.11, n = 5; P = 0.001). In MT330 tumors, P(tumor) (0.78 +/- 0.26, n = 6) and P(contralateral) (0.42 +/- 0.11, n = 5) also differed significantly (P = 0.013). Because both tumor models had disrupted blood-brain barriers and similar P(tumor) values, we used U87 and a steady-state drug administration approach to characterize the effect of gefitinib on topotecan P(tumor). At equivalent plasma topotecan exposures, we found that P(tumor) after gefitinib administration was lower. In a separate cohort of animals, we determined the volume of distribution of unbound topotecan in tumor (V(u,tumor)) and found that it was significantly higher in groups receiving gefitinib, implying that gefitinib administration leads to a greater proportion of intracellular topotecan. Our results provide crucial insights into the role that transporters play in central nervous system drug penetration and provide a better understanding of the effect of coadministration of transporter modulators on anticancer drug distribution within a tumor.
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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.