ArticleCancer research2020
Clonal ZEB1-Driven Mesenchymal Transition Promotes Targetable Oncologic Antiangiogenic Therapy Resistance.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Blood-Based Biomarkers for Glioma in the Context of Gliomagenesis: A Systematic Review.Frontiers in oncology · 2021Pooled it
- Hydrogel Microdroplet Based Glioblastoma Drug Screening Platform.Journal of biomedical materials research. Part A · 2026Article
- The glioblastoma ecosystem: clonal evolution, heterogeneity, and therapeutic resistance.Frontiers in cell and developmental biology · 2026Review
- Identification of SAMD9 as an adaptive response gene to environmental changes and its association with overall survival and immunotherapeutic response in glioblastoma.Cancer cell international · 2025Article
- Liposomal honokiol enhance the anti-tumor effect of bevacizumab in glioblastoma by inhibiting autophagy.Future science OA · 2025Article
- Single-cell sequencing analysis reveals the promotion of ELR CXCL genes on angiogenesis and the influence on malignant progression in glioblastoma.Journal of clinical biochemistry and nutrition · 2025Article
- Differential Effects of Snail-KO in Human Breast Epithelial Cells and Human Breast Epithelial × Human Breast Cancer Hybrids.International journal of molecular sciences · 2025Article
- Hydrogel microdroplet based glioblastoma drug screening platform.bioRxiv : the preprint server for biology · 2025Article
- Targeting tGLI1, a novel mediator of tumor therapeutic resistance, using Ketoconazole sensitizes glioblastoma to CDK4/6 therapy and chemoradiation.bioRxiv : the preprint server for biology · 2025Article
- Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma.Cell reports · 2025Article
- Treatment mechanism and research progress of bevacizumab for glioblastoma.American journal of cancer research · 2025Review
- SB218078 inhibits angiogenesis and epithelial-mesenchymal transition in breast cancer.Frontiers in pharmacology · 2025Article
- Real-world adverse event profile and signal characteristics of bevacizumab in glioma: a FAERS-based disproportionality analysis.Frontiers in pharmacology · 2025Article
- Viscoelastic High-Molecular-Weight Hyaluronic Acid Hydrogels Support Rapid Glioblastoma Cell Invasion with Leader-Follower Dynamics.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- Functional profiling of murine glioma models highlights targetable immune evasion phenotypes.Acta neuropathologica · 2024Article
- Collagen VI deposition primes the glioblastoma microenvironment for invasion through mechanostimulation of β-catenin signaling.PNAS nexus · 2024Article
- The tumour microenvironment, treatment resistance and recurrence in glioblastoma.Journal of translational medicine · 2024Review
- Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes.Neuro-oncology · 2024Article
- Milestones in tumor vascularization and its therapeutic targeting.Nature cancer · 2024Review
- Divergent transcriptomic signatures from putative mesenchymal stimuli in glioblastoma cells.Cancer gene therapy · 2024Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Glioblastoma (GBM) responses to bevacizumab are invariably transient with acquired resistance. We profiled paired patient specimens and bevacizumab-resistant xenograft models pre- and post-resistance toward the primary goal of identifying regulators whose targeting could prolong the therapeutic window, and the secondary goal of identifying biomarkers of therapeutic window closure. Bevacizumab-resistant patient specimens and xenografts exhibited decreased vessel density and increased hypoxia versus pre-resistance, suggesting that resistance occurs despite effective therapeutic devascularization. Microarray analysis revealed upregulated mesenchymal genes in resistant tumors correlating with bevacizumab treatment duration and causing three changes enabling resistant tumor growth in hypoxia. First, perivascular invasiveness along remaining blood vessels, which co-opts vessels in a VEGF-independent and neoangiogenesis-independent manner, was upregulated in novel biomimetic 3D bioengineered platforms modeling the bevacizumab-resistant microenvironment. Second, tumor-initiating stem cells housed in the perivascular niche close to remaining blood vessels were enriched. Third, metabolic reprogramming assessed through real-time bioenergetic measurement and metabolomics upregulated glycolysis and suppressed oxidative phosphorylation. Single-cell sequencing of bevacizumab-resistant patient GBMs confirmed upregulated mesenchymal genes, particularly glycoprotein YKL-40 and transcription factor ZEB1, in later clones, implicating these changes as treatment-induced. Serum YKL-40 was elevated in bevacizumab-resistant versus bevacizumab-naïve patients. CRISPR and pharmacologic targeting of ZEB1 with honokiol reversed the mesenchymal gene expression and associated stem cell, invasion, and metabolic changes defining resistance. Honokiol caused greater cell death in bevacizumab-resistant than bevacizumab-responsive tumor cells, with surviving cells losing mesenchymal morphology. Employing YKL-40 as a resistance biomarker and ZEB1 as a target to prevent resistance could fulfill the promise of antiangiogenic therapy. SIGNIFICANCE: Bevacizumab resistance in GBM is associated with mesenchymal/glycolytic shifts involving YKL-40 and ZEB1. Targeting ZEB1 reduces bevacizumab-resistant GBM phenotypes. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/7/1498/F1.large.jpg.
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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.