Trial reportScientific reports2015
Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.
Trial report in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Glasdegib in combination with temozolomide and radiotherapy in adult patients with newly diagnosed glioblastoma: the phase Ib/II GEINO 1602 trial.Nature communications · 2025Trial
- In Vitro Functional Validation of an Anti-FREM2 Nanobody for Glioblastoma Cell Targeting.Antibodies (Basel, Switzerland) · 2025Article
- Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer.Scientific reports · 2024Article
- Correlation analysis of tumor purity with clinicopathological, molecular, and imaging features in high-grade gliomas.Neurosurgical review · 2022Article
- Knockdown of DEPDC1B inhibits the development of glioblastoma.Cancer cell international · 2020Article
- HighCancers · 2019Article
- Polyethylenimine-Spherical Nucleic Acid Nanoparticles against Gli1 Reduce the Chemoresistance and Stemness of Glioblastoma Cells.Molecular pharmaceutics · 2018Article
- Investigating the role of Hedgehog/GLI1 signaling in glioblastoma cell response to temozolomide.Oncotarget · 2018Article
- Blocking epithelial-to-mesenchymal transition in glioblastoma with a sextet of repurposed drugs: the EIS regimen.Oncotarget · 2017Article
- BREAST CANCER HISTOPATHOLOGY IMAGE ANALYSIS PIPELINE FOR TUMOR PURITY ESTIMATION.Proceedings. IEEE International Symposium on Biomedical Imaging · 2017Article
- Multiple roles of Ulk4 in neurogenesis and brain function.Neurogenesis (Austin, Tex.) · 2017Article
- Autophagy stimulation abrogates herpes simplex virus-1 infection.Scientific reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy.
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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.