ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Prolonged inhibition of glioblastoma xenograft initiation and clonogenic growth following in vivo Notch blockade.
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 33 papers.
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Who cites it
33 citing papers in PubMed.
- Systemic cyst(e)inase administration induces ferroptosis and synergizes with temozolomide in glioblastoma.iScience · 2026Article
- Transcriptomic Comparisons of Somatic and Cancer Stem Cells.Biomedicines · 2025Review
- Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.Life (Basel, Switzerland) · 2025Review
- Diffuse intrinsic pontine glioma (DIPG): A review of current and emerging treatment strategies.Cancer letters · 2024Review
- Therapeutic vulnerabilities of cancer stem cells and effects of natural products.Natural product reports · 2023Review
- Regulation of Cell Plasticity by Bromodomain and Extraterminal Domain (BET) Proteins: A New Perspective in Glioblastoma Therapy.International journal of molecular sciences · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Article
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- RASSF1A disrupts the NOTCH signaling axis via SNURF/RNF4-mediated ubiquitination of HES1.EMBO reports · 2022Article
- Aberrant Notch signaling in gliomas: a potential landscape of actionable converging targets for combination approach in therapies resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Emerging role of tumor cell plasticity in modifying therapeutic response.Signal transduction and targeted therapy · 2020Review
- Targeting cancer stem cells in squamous cell carcinoma.Precision clinical medicine · 2019Review
- Notch1 signaling pathway promotes invasion, self-renewal and growth of glioma initiating cells via modulating chemokine system CXCL12/CXCR4.Journal of experimental & clinical cancer research : CR · 2019Article
- Modulation of mitochondrial DNA copy number in a model of glioblastoma induces changes to DNA methylation and gene expression of the nuclear genome in tumours.Epigenetics & chromatin · 2018Article
- Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells.Journal of visualized experiments : JoVE · 2018Article
- Targeting Notch signalling pathway of cancer stem cells.Stem cell investigation · 2018Review
- An immunocompetent mouse model of human glioblastoma.Oncotarget · 2017Article
- Notch1 regulates the JNK signaling pathway and increases apoptosis in hepatocellular carcinoma.Oncotarget · 2017Article
- Disruption of the monocarboxylate transporter-4-basigin interaction inhibits the hypoxic response, proliferation, and tumor progression.Scientific reports · 2017Article
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Authors and funding
5 authors.
Funding
Abstract
purposeTo examine the effects of clinically relevant pharmacologic Notch inhibition on glioblastoma xenografts. EXPERIMENTAL
designMurine orthotopic xenografts generated from temozolomide-sensitive and -resistant glioblastoma neurosphere lines were treated with the γ-secretase inhibitor MRK003. Tumor growth was tracked by weekly imaging, and the effects on animal survival and tumor proliferation were assessed, along with the expression of Notch targets, stem cell, and differentiation markers, and the biology of neurospheres isolated from previously treated xenografts and controls.
resultsWeekly MRK003 therapy resulted in significant reductions in growth as measured by imaging, as well as prolongation of survival. Microscopic examination confirmed a statistically significant reduction in cross-sectional tumor area and mitotic index in a MRK003-treated cohort as compared with controls. Expression of multiple Notch targets was reduced in the xenografts, along with neural stem/progenitor cell markers, whereas glial differentiation was induced. Neurospheres derived from MRK003-treated xenografts exhibited reduced clonogenicity and formed less aggressive secondary xenografts. Neurospheres isolated from treated xenografts remained sensitive to MRK003, suggesting that therapeutic resistance does not rapidly arise during in vivo Notch blockade.
conclusionsWeekly oral delivery of MRK003 results in significant in vivo inhibition of Notch pathway activity, tumor growth, stem cell marker expression, and clonogenicity, providing preclinical support for the use of such compounds in patients with malignant brain tumors. Some of these effects can persist for some time after in vivo therapy is complete.
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