ArticleJournal of neuro-oncology2020
Preclinical evaluation of binimetinib (MEK162) delivered via polymeric nanocarriers in combination with radiation and temozolomide in glioma.
Article in Journal of neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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.
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
12 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024Review
- Nano-radiopharmaceuticals as therapeutic agents.Frontiers in medicine · 2024Review
- Capicua (CIC) mutations in gliomas in association with MAPK activation for exposing a potential therapeutic target.Medical oncology (Northwood, London, England) · 2023Article
- The Nanotechnology-Based Approaches against Kirsten Rat Sarcoma-Mutated Cancers.Pharmaceutics · 2023Review
- Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models.Scientific reports · 2023Article
- De Novo Self-Assembling Peptides Mediate the Conversion of Temozolomide and Delivery of a Model Drug into Glioblastoma Multiforme Cells.Biomedicines · 2022Article
- Review
- Advances of Nanomedicine in Radiotherapy.Pharmaceutics · 2021Review
- Experimental and clinical studies on radiation and curcumin in human glioma.Journal of cancer research and clinical oncology · 2021Article
- LRP1-mediated pH-sensitive polymersomes facilitate combination therapy of glioblastoma in vitro and in vivo.Journal of nanobiotechnology · 2021Article
- Role of Polymeric Local Drug Delivery in Multimodal Treatment of Malignant Glioma: A Review.International journal of nanomedicine · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeGlioblastoma multiforme (GBM) is the most aggressive subtype of malignant gliomas, with an average survival rate of 15 months after diagnosis. More than 90% of all GBMs have activating mutations in the MAPK/ERK pathway. Recently, we showed the allosteric MEK1/2 inhibitor binimetinib (MEK162) to inhibit cell proliferation and to enhance the effect of radiation in preclinical human GBM models. Because the free drug cannot pass the blood-brain barrier (BBB), we investigated the use of nanocarriers for transport of the drug through the BBB and its efficacy when combined with radiotherapy and temozolomide (TMZ) in glioma spheroids.
methodsIn vitro studies were performed using multicellular U87 human GBM spheroids. Polymeric nanocarriers (polymersomes) were loaded with MEK162. The interaction between nanocarrier delivered MEK162, irradiation and TMZ was studied on the kinetics of spheroid growth and on protein expression in the MAPK/ERK pathway. BBB passaging was evaluated in a transwell system with human cerebral microvascular endothelial (hCMEC/D3) cells.
resultsMEK162 loaded polymersomes inhibited spheroid growth. A synergistic effect was found in combination with fractionated irradiation and an additive effect with TMZ on spheroid volume reduction. Fluorescent labeled polymersomes were taken up by human cerebral microvascular endothelial cells and passed the BBB in vitro.
conclusionMEK162 loaded polymersomes are taken up by multicellular spheroids. The nanocarrier delivered drug reduced spheroid growth and inhibited its molecular target. MEK162 delivered via polymersomes showed interaction with irradiation and TMZ. The polymersomes crossed the in vitro BBB model and therewith offer exciting challenges ahead for delivery of therapeutics agents to brain tumours.
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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.