ArticleJournal of experimental & clinical cancer research : CR2021
Chlorpromazine induces cytotoxic autophagy in glioblastoma cells via endoplasmic reticulum stress and unfolded protein response.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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
37 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 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
- Repurposing Antipsychotics in Cancer Therapy: Modulation of Autophagy Mechanisms.Clinical drug investigation · 2026Review
- Unfolded Protein Response in Glioblastoma: Mechanisms of Proteostasis, Tumor Adaptation, and Therapeutic Relevance.Neurochemical research · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Network-driven prioritization and functional phenotyping nominate TTC23 as a biomarker-informed target in chlorpromazine repurposing for glioblastoma.Frontiers in pharmacology · 2026Article
- Chlorpromazine activates cGAS-STING signaling and reprograms the immune response in glioblastoma.Frontiers in immunology · 2026Article
- Integrated screening for small molecules interfering with PKM2: a drug repurposing strategy against glioblastoma.Journal of translational medicine · 2025Article
- Liposomal honokiol enhance the anti-tumor effect of bevacizumab in glioblastoma by inhibiting autophagy.Future science OA · 2025Article
- Antipsychotic Chlorpromazine Suppresses STAT5 Signaling, Overcomes Resistance Mediated by the Gatekeeper Mutation FLT3-ITD/F691L, and Synergizes with Quizartinib in FLT3-ITD-Positive Cells.Current issues in molecular biology · 2025Article
- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Nanomedicine Approaches for Autophagy Modulation in Cancer Therapy.Small science · 2025Article
- Evidence for cytoprotective autophagy in response to HER2-targeted monoclonal antibodies.The Journal of pharmacology and experimental therapeutics · 2025Review
- Enhancement of chlorpromazine efficacy in breast cancer treatment by 266 nm laser irradiation.Scientific reports · 2024Article
- Chlorpromazine overcomes temozolomide resistance in glioblastoma by inhibiting Cx43 and essential DNA repair pathways.Journal of translational medicine · 2024Article
- The unfolded protein response machinery in glioblastoma genesis, chemoresistance and as a druggable target.CNS neuroscience & therapeutics · 2024Review
- Antipsychotics possess anti-glioblastoma activity by disrupting lysosomal function and inhibiting oncogenic signaling by stabilizing PTEN.Cell death & disease · 2024Article
- New Salicylanilide Derivatives and Their Peptide Conjugates as Anticancer Compounds: Synthesis, Characterization, andACS omega · 2024Article
- Insomnia in Forensic Detainees: Is Salience Network the Common Pathway for Sleep, Neuropsychiatric, and Neurodegenerative Disorders?Journal of clinical medicine · 2024Review
- Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.Current issues in molecular biology · 2024Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundGlioblastoma (GBM; grade IV glioma) is characterized by a very short overall survival time and extremely low 5-year survival rates. We intend to promote experimental and clinical research on rationale and scientifically driven drug repurposing. This may represent a safe and often inexpensive way to propose novel pharmacological approaches to GBM. Our precedent work describes the role of chlorpromazine (CPZ) in hindering malignant features of GBM. Here, we investigate in greater detail the molecular mechanisms at the basis of the effect of CPZ on GBM cells.
methodsWe employed proteomics platforms, i.e., activity-based protein profiling plus mass spectrometry, to identify potential cellular targets of the drug. Then, by means of established molecular and cellular biology techniques, we assessed the effects of this drug on GBM cell metabolic and survival pathways.
resultsThe experimental output indicated as putative targets of CPZ several of factors implicated in endoplasmic reticulum (ER) stress, with consequent unfolded protein response (UPR). Such a perturbation culminated in a noticeable reactive oxygen species generation and intense autophagic response that resulted in cytotoxic and abortive effects for six GBM cell lines, three of which growing as neurospheres, while it appeared cytoprotective for the RPE-1 human non-cancer neuro-ectodermal cell line.
conclusionsThis discrepancy could be central in explaining the lethal effects of the drug on GBM cells and the relatively scarce cytotoxicity toward normal tissues attributed to this compound. The data presented here offer support to the multicenter phase II clinical trial we have undertaken, which consists of the addition of CPZ to first-line treatment of GBM patients carrying a hypo- or un-methylated MGMT gene, i.e. those characterized by intrinsic resistance to temozolomide.
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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.