ArticleNeuro-oncology2018
Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha.
Article in Neuro-oncology, 2018. 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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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.
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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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Nanotechnology in neurosurgery: a systematic review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Pooled it
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- IGSF11-VISTA is a critical and targetable immune checkpoint axis in diffuse midline glioma.Cancer cell · 2026Article
- Modulators of Diacylglycerol Kinase Activity: A Review of Advances and Challenges.Medicinal research reviews · 2026Review
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- BNIP3-mTOR Signaling Mediates Resistance to MET Inhibition in Glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- Saturated fatty acid- and/or monounsaturated fatty acid-containing-phosphatidic acids selectively interact with and activate phosphoglycerate mutase 1.Biochemistry and biophysics reports · 2025Article
- Medulloblastoma: biology and immunotherapy.Frontiers in immunology · 2025Review
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- Dual p38MAPK and MEK inhibition disrupts adaptive chemoresistance in mesenchymal glioblastoma to temozolomide.Neuro-oncology · 2024Article
- Divergent transcriptomic signatures from putative mesenchymal stimuli in glioblastoma cells.Cancer gene therapy · 2024Article
- Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma.Cancer communications (London, England) · 2024Article
- HSPA5 and FGFR1 genes in the mesenchymal subtype of glioblastoma can improve a treatment efficacy.Animal cells and systems · 2024Article
- Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway.Discover oncology · 2023Article
- Role of Diacylglycerol Kinases in Acute Myeloid Leukemia.Biomedicines · 2023Article
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- Predicting small molecule binding pockets on diacylglycerol kinases using chemoproteomics and AlphaFold.RSC chemical biology · 2023Article
- Targeting diacylglycerol kinase α impairs lung tumorigenesis by inhibiting cyclin D3.Thoracic cancer · 2023Article
- Proton boron capture therapy (PBCT) induces cell death and mitophagy in a heterotopic glioblastoma model.Communications biology · 2023Article
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
Background: The mesenchymal phenotype in glioblastoma (GBM) and other cancers drives aggressiveness and treatment resistance, leading to therapeutic failure and recurrence of disease. Currently, there is no successful treatment option available against the mesenchymal phenotype. Methods: We classified patient-derived GBM stem cell lines into 3 subtypes: proneural, mesenchymal, and other/classical. Each subtype's response to the inhibition of diacylglycerol kinase alpha (DGKα) was compared both in vitro and in vivo. RhoA activation, liposome binding, immunoblot, and kinase assays were utilized to elucidate the novel link between DGKα and geranylgeranyltransferase I (GGTase I). Results: Here we show that inhibition of DGKα with a small-molecule inhibitor, ritanserin, or RNA interference preferentially targets the mesenchymal subtype of GBM. We show that the mesenchymal phenotype creates the sensitivity to DGKα inhibition; shifting GBM cells from the proneural to the mesenchymal subtype increases ritanserin activity, with similar effects in epithelial-mesenchymal transition models of lung and pancreatic carcinoma. This enhanced sensitivity of mesenchymal cancer cells to ritanserin is through inhibition of GGTase I and downstream mediators previously associated with the mesenchymal cancer phenotype, including RhoA and nuclear factor-kappaB. DGKα inhibition is synergistic with both radiation and imatinib, a drug preferentially affecting proneural GBM. Conclusions: Our findings demonstrate that a DGKα-GGTase I pathway can be targeted to combat the treatment-resistant mesenchymal cancer phenotype. Combining therapies with greater activity against each GBM subtype may represent a viable therapeutic option against 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.