ArticleCancer research2012
Resistance of glioblastoma-initiating cells to radiation mediated by the tumor microenvironment can be abolished by inhibiting transforming growth factor-β.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.
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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
141 citing papers in PubMed, 1 synthesis or guideline pooled it, 237 citations in OpenAlex.
- Mechanisms of traditional Chinese medicine overcoming of radiotherapy resistance in breast cancer.Frontiers in oncology · 2024Pooled it
- Butyl and isobutyl ortho-coumaric acid derivatives reduce self-renewal and MGMT expression in GBM cells with stem cell-like characteristicsBiomolecules & biomedicine · 2026Article
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- Pulsed Low-Dose-Rate Chemoradiation Induces Stromal Reprogramming in Pancreatic CAF-Generated ECM: Quantification by the HOST-Factor.Gastro hep advances · 2026Article
- Radioresistance Mechanisms in Head and Neck Cancer.Clinical and experimental otorhinolaryngology · 2025Review
- Immune factors and their role in tumor aggressiveness in glioblastoma: Atypical cadherin FAT1 as a promising target for combating immune evasion.Cellular & molecular biology letters · 2025Review
- Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response.Nature reviews. Cancer · 2025Review
- Comprehensive review of the resistance mechanisms of colorectal cancer classified by therapy type.Frontiers in immunology · 2025Review
- Dissecting TGF-β-induced glioblastoma invasion with engineered hyaluronic acid hydrogels.APL bioengineering · 2024Article
- RAPID resistance to BET inhibitors is mediated by FGFR1 in glioblastoma.Scientific reports · 2024Article
- Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy.iScience · 2024Article
- Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma.Cancers · 2023Review
- Radiation dose, schedule, and novel systemic targets for radio-immunotherapy combinations.Journal of the National Cancer Institute · 2023Article
- Radiotherapy and radio-sensitization in H3CNS neuroscience & therapeutics · 2023Review
- The Glioblastoma Landscape: Hallmarks of Disease, Therapeutic Resistance, and Treatment Opportunities.Medical research archives · 2023Article
- Molecular mechanisms of tumor resistance to radiotherapy.Molecular cancer · 2023Review
- Molecular Pathways and Mechanisms of TGFβ in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Immunological and tumor-intrinsic mechanisms mediate the synergistic growth suppression of experimental glioblastoma by radiotherapy and MET inhibition.Acta neuropathologica communications · 2023Article
- Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.Neoplasia (New York, N.Y.) · 2023Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The poor prognosis of glioblastoma (GBM) routinely treated with ionizing radiation (IR) has been attributed to the relative radioresistance of glioma-initiating cells (GIC). Other studies indicate that although GIC are sensitive, the response is mediated by undefined factors in the microenvironment. GBM produce abundant transforming growth factor-β (TGF-β), a pleotropic cytokine that promotes effective DNA damage response. Consistent with this, radiation sensitivity, as measured by clonogenic assay of cultured murine (GL261) and human (U251, U87MG) glioma cell lines, increased by approximately 25% when treated with LY364947, a small-molecule inhibitor of TGF-β type I receptor kinase, before irradiation. Mice bearing GL261 flank tumors treated with 1D11, a pan-isoform TGF-β neutralizing antibody, exhibited significantly increased tumor growth delay following IR. GL261 neurosphere cultures were used to evaluate GIC. LY364947 had no effect on the primary or secondary neurosphere-forming capacity. IR decreased primary neurosphere formation by 28%, but did not reduce secondary neurosphere formation. In contrast, LY364947 treatment before IR decreased primary neurosphere formation by 75% and secondary neurosphere formation by 68%. Notably, GL261 neurospheres produced 3.7-fold more TGF-β per cell compared with conventional culture, suggesting that TGF-β production by GIC promotes effective DNA damage response and self-renewal, which creates microenvironment-mediated resistance. Consistent with this, LY364947 treatment in irradiated GL261 neurosphere-derived cells decreased DNA damage responses, H2AX and p53 phosphorylation, and induction of self-renewal signals, Notch1 and CXCR4. These data motivate the use of TGF-β inhibitors with radiation to improve therapeutic response in patients with GBM.
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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.