ArticleOncotarget2017
Metabolic targeting of EGFRvIII/PDK1 axis in temozolomide resistant glioblastoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05120284 (Trial of Dichloroacetate), which is not on this map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM)
Who cites it
30 citing papers in PubMed, 35 citations in OpenAlex.
- Establishing PDK1-based prognostic biomarkers and identifying targeted inhibitors for glioma prognosis and therapy.BMC neurology · 2026Article
- Glioblastoma cells that evade chemoradiotherapy-induced cell death exhibit a bifurcated glycolytic program.Cell death & disease · 2026Article
- Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review).Molecular and clinical oncology · 2026Review
- In Vivo and In Vitro Experimental Study Comparing the Effect of a Combination of Sodium Dichloroacetate and Valproic Acid with That of Temozolomide on Adult Glioblastoma.International journal of molecular sciences · 2025Article
- Disease stage-specific role of the mitochondrial pyruvate carrier suppresses differentiation in temozolomide and radiation-treated glioblastoma.Neuro-oncology · 2025Article
- Targeting metabolic reprogramming in glioblastoma as a new strategy to overcome therapy resistance.Frontiers in cell and developmental biology · 2025Review
- Identification of STAM-binding protein as a target for the treatment of gemcitabine resistance pancreatic cancer in a nutrient-poor microenvironment.Cell death & disease · 2024Article
- Identifying Diffuse Glioma Subtypes Based on Pathway Enrichment Evaluation.Interdisciplinary sciences, computational life sciences · 2024Article
- From signalling pathways to targeted therapies: unravelling glioblastoma's secrets and harnessing two decades of progress.Signal transduction and targeted therapy · 2023Review
- Article
- Identification of potential targets of the curcumin analog CCA-1.1 for glioblastoma treatment : integrated computational analysis and in vitro study.Scientific reports · 2022Article
- Galectin-1 activates carbonic anhydrase IX and modulates glioma metabolism.Cell death & disease · 2022Article
- Alterations in Molecular Profiles Affecting Glioblastoma Resistance to Radiochemotherapy: Where Does the Good Go?Cancers · 2022Review
- Review
- Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells.International journal of molecular sciences · 2021Article
- Phosphorylated form of pyruvate dehydrogenase α1 mediates tumor necrosis factor α-induced glioma cell migration.Oncology letters · 2021Article
- Article
- Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Phosphoinositide-dependent Kinase-1 (PDPK1) regulates serum/glucocorticoid-regulated Kinase 3 (SGK3) for prostate cancer cell survival.Journal of cellular and molecular medicine · 2020Article
- OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation.Nature communications · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastomas are characterized by amplification of EGFR. Approximately half of tumors with EGFR over-expression also express a constitutively active ligand independent EGFR variant III (EGFRvIII). While current treatments emphasize surgery followed by radiation and chemotherapy with Temozolomide (TMZ), acquired chemoresistance is a universal feature of recurrent GBMs. To mimic the GBM resistant state, we generated an in vitro TMZ resistant model and demonstrated that dichloroacetate (DCA), a metabolic inhibitor of pyruvate dehydrogenase kinase 1 (PDK1), reverses the Warburg effect. Microarray analysis conducted on the TMZ resistant cells with their subsequent treatment with DCA revealed PDK1 as its sole target. DCA treatment also induced mitochondrial membrane potential change and apoptosis as evidenced by JC-1 staining and electron microscopic studies. Computational homology modeling and docking studies confirmed DCA binding to EGFR, EGFRvIII and PDK1 with high affinity. In addition, expression of EGFRvIII was comparable to PDK1 when compared to EGFR in GBM surgical specimens supporting our in silico prediction data. Collectively our current study provides the first in vitro proof of concept that DCA reverses the Warburg effect in the setting of EGFRvIII positivity and TMZ resistance leading to GBM cytotoxicity, implicating cellular tyrosine kinase signaling in cancer cell metabolism.
Indexed as
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What OpenQuestion holds
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.