ArticleOncotarget2014
Genome-wide shRNA screen revealed integrated mitogenic signaling between dopamine receptor D2 (DRD2) and epidermal growth factor receptor (EGFR) in glioblastoma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
109 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Repurposing neurological drugs for brain cancer therapeutics: A systematic approach to identify charged molecules for affinity-based local drug delivery systems.International journal of pharmaceutics · 2025Pooled it
- Depression and glioblastoma, complicated concomitant diseases: a systemic review of published literature.Neurosurgical review · 2020Pooled it
- Biological activity of weekly ONC201 in adult recurrent glioblastoma patients.Neuro-oncology · 2020Trial
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- Repurposing Antipsychotic Agents in Oncology: Mechanistic Rationale, Emerging Evidence, and Therapeutic Potential.Cancers · 2026Review
- The GPCR Connection: Linking Alzheimer's Disease and Glioblastoma.Journal of cellular and molecular medicine · 2026Review
- Pharmacologic targeting of the dopamine D2 receptor impacts the efficacy of immune checkpoint blockade in melanoma.Journal for immunotherapy of cancer · 2026Article
- Spirohydantoin derivatives exert dopamine DScientific reports · 2026Article
- Pathological neural and immune synapses in glioblastoma progression: mechanisms and therapeutic opportunities.Frontiers in neural circuits · 2026Review
- Neurotransmitter-Mediated Signaling in Glioblastoma and Glial Tumors: Biology and Therapeutic Opportunities.Oncology research · 2026Review
- Long-term survival in glioblastoma patients treated with dopamine agonists: A report of two cases and implications for drug repurposing.Surgical neurology international · 2026Article
- Small-Molecule Drugs in Pediatric Neuro-Oncology.Current oncology (Toronto, Ont.) · 2025Review
- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies.Molecular cancer · 2025Review
- The Role of the Gut Microbiota in Modulating Signaling Pathways and Oxidative Stress in Glioma Therapies.Cancers · 2025Review
- Hijacking of the nervous system in cancer: mechanism and therapeutic targets.Molecular cancer · 2025Review
- The role of the nervous system in the occurrence, development, and immune response of renal cell carcinoma.Frontiers in immunology · 2025Review
- Widespread neuroanatomical integration and distinct electrophysiological properties of glioma-innervating neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting Mitochondria in Glioma: New Hopes for a Cure.Biomedicines · 2024Review
- Therapeutic strategies for colorectal cancer: antitumor efficacy of dopamine D2 receptor antagonists.Toxicological research · 2024Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Glioblastoma remains one of the deadliest of human cancers, with most patients succumbing to the disease within two years of diagnosis. The available data suggest that simultaneous inactivation of critical nodes within the glioblastoma molecular circuitry will be required for meaningful clinical efficacy. We conducted parallel genome-wide shRNA screens to identify such nodes and uncovered a number of G-Protein Coupled Receptor (GPCR) neurotransmitter pathways, including the Dopamine Receptor D2 (DRD2) signaling pathway. Supporting the importance of DRD2 in glioblastoma, DRD2 mRNA and protein expression were elevated in clinical glioblastoma specimens relative to matched non-neoplastic cerebrum. Treatment with independent si-/shRNAs against DRD2 or with DRD2 antagonists suppressed the growth of patient-derived glioblastoma lines both in vitro and in vivo. Importantly, glioblastoma lines derived from independent genetically engineered mouse models (GEMMs) were more sensitive to haloperidol, an FDA approved DRD2 antagonist, than the premalignant astrocyte lines by approximately an order of magnitude. The pro-proliferative effect of DRD2 was, in part, mediated through a GNAI2/Rap1/Ras/ERK signaling axis. Combined inhibition of DRD2 and Epidermal Growth Factor Receptor (EGFR) led to synergistic tumoricidal activity as well as ERK suppression in independent in vivo and in vitro glioblastoma models. Our results suggest combined EGFR and DRD2 inhibition as a promising strategy for glioblastoma treatment.
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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.