ArticleCancer research2014
Hedgehog signaling drives radioresistance and stroma-driven tumor repopulation in head and neck squamous cancers.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06416436 (Immunotherapy in Combination With Ablative Radiosurgery to Ultra-high DoSes), which is not on this map. Cited by 45 papers.
What it found
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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.
Immunotherapy in Combination With Ablative Radiosurgery to Ultra-high DoSes (ICARUS): A Phase I Dose-escalation Radiosurgery Study in Metastatic Cancers
Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma.Nature communications · 2022Trial
- [Molecular cancer · 2026Article
- Deciphering the prognostic potential of a necroptosis-related gene signature in head and neck squamous cell carcinoma: a bioinformatic analysis.Translational cancer research · 2025Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.Science advances · 2024Article
- A Pilot Immunohistochemical Study Identifies Hedgehog Pathway Expression in Sinonasal Adenocarcinoma.International journal of molecular sciences · 2024Article
- Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature.Scientific reports · 2024Article
- Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.Theranostics · 2024Review
- New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Review
- Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Hedgehog signaling and the glioma-associated oncogene in cancer radioresistance.Frontiers in cell and developmental biology · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Integrated radiogenomics analyses allow for subtype classification and improved outcome prognosis of patients with locally advanced HNSCC.Scientific reports · 2022Article
- Antagonizing Glutamine Bioavailability Promotes Radiation Sensitivity in Prostate Cancer.Cancers · 2022Article
- Mitogen-activated protein kinase-activated protein kinase-2 (MK2) and its role in cell survival, inflammatory signaling, and migration in promoting cancer.Molecular carcinogenesis · 2022Article
- Proton pump inhibitors and sensitization of cancer cells to radiation therapy.Frontiers in oncology · 2022Review
- Phytochemicals: Potential Therapeutic Modulators of Radiation Induced Signaling Pathways.Antioxidants (Basel, Switzerland) · 2021Review
- The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Local control and overall survival in patients with advanced head and neck squamous cell cancer (HNSCC) remains dismal. Signaling through the Hedgehog (Hh) pathway is associated with epithelial-to-mesenchymal transition, and activation of the Hh effector transcription factor Gli1 is a poor prognostic factor in this disease setting. Here, we report that increased GLI1 expression in the leading edge of HNSCC tumors is further increased by irradiation, where it contributes to therapeutic inhibition. Hh pathway blockade with cyclopamine suppressed GLI1 activation and enhanced tumor sensitivity to radiotherapy. Furthermore, radiotherapy-induced GLI1 expression was mediated in part by the mTOR/S6K1 pathway. Stroma exposed to radiotherapy promoted rapid tumor repopulation, and this effect was suppressed by Hh inhibition. Our results demonstrate that Gli1 that is upregulated at the tumor-stroma intersection in HNSCC is elevated by radiotherapy, where it contributes to stromal-mediated resistance, and that Hh inhibitors offer a rational strategy to reverse this process to sensitize HNSCC to radiotherapy.
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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.