{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:02:54Z","timestamp":1789707774415,"version":"4.0.1"},"reference-count":123,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Edward Via College of Osteopathic Medicine","award":["26-0029"],"award-info":[{"award-number":["26-0029"]}],"id":[{"id":"https:\/\/ror.org\/00sda2672","id-type":"ROR","asserted-by":"crossref"}]},{"award":["26-0029"],"award-info":[{"award-number":["26-0029"]}],"id":[{"id":"https:\/\/ror.org\/00sda2672","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Antipsychotic agents\u2014spanning first-, second-, and third-generation drug classes\u2014are emerging as mechanistically diverse candidates for repurposing in oncology. Although developed to modulate dopaminergic and serotonergic neurotransmission, some of these compounds exert pleiotropic effects on cancer cell survival, metabolism, and stemness. Across multiple malignancies, antipsychotics disrupt oncogenic signaling networks including PI3K\/Akt\/mTOR, STAT3\/5, MAPK\/ERK, and Wnt\/\u03b2-Catenin, impair lysosomal and autophagic flux, and induce mitochondrial and calcium-dependent metabolic stress. Notably, several phenothiazines and dopamine-modulating agents selectively reduce cancer stem cell populations, suggesting potential utility in limiting recurrence and mitigating therapeutic resistance. These effects appear to involve disruption of CSC signaling pathways and interference with dopamine-dependent mechanisms that support stemness and survival. Preclinical studies consistently demonstrate antiproliferative, proapoptotic, antimetastatic, and chemosensitizing effects, whereas early clinical investigations demonstrate target engagement and feasibility but do not establish anticancer efficacy. Clinical trials of thioridazine in acute myeloid leukemia and chlorpromazine in glioblastoma show evidence of pharmacodynamic activity in patients, though these findings remain preliminary and non-efficacy-based. However, translation remains constrained by dose-limiting toxicities, pharmacokinetic barriers, and conflicting epidemiologic signals regarding long-term carcinogenic risk. Here, we synthesize mechanistic, translational, and emerging clinical findings relevant to antipsychotic repurposing in oncology, highlight tumor contexts in which these agents may hold potential, and outline future directions including biomarker-guided patient selection, rational combination strategies, and artificial intelligence (AI)-enabled drug-repurposing pipelines. Collectively, antipsychotics represent a promising yet underexplored class of multi-targeted agents; to define their full therapeutic potential will require rigorous mechanistic validation and carefully designed clinical trials.<\/jats:p>","DOI":"10.3390\/cancers18182992","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:06:37Z","timestamp":1789549597000},"page":"2992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing Antipsychotic Agents in Oncology: Mechanistic Rationale, Emerging Evidence, and Therapeutic Potential"],"prefix":"10.3390","volume":"18","author":[{"given":"Adina","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-8570","authenticated-orcid":false,"given":"Sahar","family":"Fattani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaiya","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haneen","family":"Hamed","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medhat S.","family":"El-Halawany","sequence":"additional","affiliation":[{"name":"Division of Natural & Computational Sciences, Texas College, Tyler, TX 75702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7150-4983","authenticated-orcid":false,"given":"Debasis","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Knoxville, TN 37932, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-3576","authenticated-orcid":false,"given":"Maysoon M.","family":"Makhlouf","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-0348","authenticated-orcid":false,"given":"Zakaria Y.","family":"Abd Elmageed","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: Progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/jat.4921","article-title":"Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review","volume":"46","author":"Otreba","year":"2026","journal-title":"J. Appl. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fan, Y.C., Lin, S.C., Lai, P.J., Lai, P.C., Maurus, G., and Chen, S.Y. (2025). A psychiatric medication, clozapine, induces autophagy and apoptosis in breast cancer cells through reactive oxygen species. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0326224"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Camuzard, O., Trojani, M.C., Santucci-Darmanin, S., Pagnotta, S., Breuil, V., Carle, G.F., and Pierrefite-Carle, V. (2020). Autophagy in Osteosarcoma Cancer Stem Cells Is Critical Process which Can Be Targeted by the Antipsychotic Drug Thioridazine. Cancers, 12.","DOI":"10.3390\/cancers12123675"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/carcin\/bgac045","article-title":"Understanding the role of dopamine in cancer: Past, present and future","volume":"43","author":"Grant","year":"2022","journal-title":"Carcinogenesis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.canlet.2018.01.058","article-title":"Repurposing psychiatric drugs as anti-cancer agents","volume":"419","author":"Huang","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vlachos, N., Lampros, M., Voulgaris, S., and Alexiou, G.A. (2021). Repurposing Antipsychotics for Cancer Treatment. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121785"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/j.1600-0447.1992.tb10325.x","article-title":"Neuroleptic medication and reduced risk of prostate cancer in schizophrenic patients","volume":"85","author":"Mortensen","year":"1992","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"de Moraes, F.C.A., Sudo, R.Y.U., Souza, M.E.C., Fernandes, M.R., and Dos Santos, N.P.C. (2024). The incidence risk of gynecological cancer by antipsychotic use: A meta-analysis of 50,402 patients. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12481-6"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1093\/carcin\/bgt169","article-title":"The antipsychotic agent chlorpromazine induces autophagic cell death by inhibiting the Akt\/mTOR pathway in human U-87MG glioma cells","volume":"34","author":"Shin","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2302413","DOI":"10.1080\/15384047.2024.2302413","article-title":"The antipsychotic drug pimozide promotes apoptosis through the RAF\/ERK pathway and enhances autophagy in breast cancer cells","volume":"25","author":"Jiang","year":"2024","journal-title":"Cancer Biol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e70076","DOI":"10.1002\/prp2.70076","article-title":"From Psychiatry to Oncology: Exploring the Anti-Neoplastic Mechanisms of Aripiprazole and Its Potential Use in Cancer Treatment","volume":"13","author":"Blum","year":"2025","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115665","DOI":"10.1016\/j.biopha.2023.115665","article-title":"Pimavanserin tartrate induces apoptosis and cytoprotective autophagy and synergizes with chemotherapy on triple negative breast cancer","volume":"168","author":"Zhang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/jat.4046","article-title":"In vitro anticancer activity of fluphenazine, perphenazine and prochlorperazine. A review","volume":"41","author":"Otreba","year":"2021","journal-title":"J. Appl. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"110772","DOI":"10.1016\/j.biopha.2020.110772","article-title":"Haloperidol in palliative care: Indications and risks","volume":"132","author":"Oduah","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Papadopoulos, F., Isihou, R., Alexiou, G.A., Tsalios, T., Vartholomatos, E., Markopoulos, G.S., Sioka, C., Tsekeris, P., Kyritsis, A.P., and Galani, V. (2020). Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120595"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.18632\/oncotarget.28010","article-title":"Multifaceted effect of chlorpromazine in cancer: Implications for cancer treatment","volume":"12","author":"Brelidze","year":"2021","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, N., Rao, L., Zhao, X., Shen, J., Su, D., Ma, G., Sun, S., Ma, Q., Zhang, L., and Dong, C. (2023). Chlorpromazine affects autophagy in association with altered Rag GTPase-mTORC1-TFEB signaling. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1266198"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1124\/mol.114.096941","article-title":"Repurposing the antipsychotic trifluoperazine as an antimetastasis agent","volume":"87","author":"Li","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.tips.2025.03.005","article-title":"Repurposing trifluoperazine for glioblastoma treatment","volume":"46","author":"Gan","year":"2025","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"118133","DOI":"10.1016\/j.bcp.2026.118133","article-title":"Targeting CDK4 with repurposing perphenazine inhibited the growth of gastric cancer AGS and HGC27 cells by arresting cell cycle","volume":"251","author":"Ma","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127239","DOI":"10.1016\/j.bmcl.2020.127239","article-title":"Repurposing of antipsychotics perphenazine for the treatment of endometrial cancer","volume":"30","author":"Chen","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1753","DOI":"10.1038\/cddis.2015.77","article-title":"Identification of thioridazine, an antipsychotic drug, as an antiglioblastoma and anticancer stem cell agent using public gene expression data","volume":"6","author":"Cheng","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.3892\/ol.2017.5651","article-title":"Thioridazine has potent antitumor effects on lung cancer stem-like cells","volume":"13","author":"Shen","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_25","first-page":"3853","article-title":"The STAT3 inhibitor pimozide impedes cell proliferation and induces ROS generation in human osteosarcoma by suppressing catalase expression","volume":"9","author":"Cai","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1182\/blood-2009-11-255232","article-title":"The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors","volume":"117","author":"Nelson","year":"2011","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jain, A., Motatis, A.K.B., Dharmashekar, C., Shreevatsa, B., Vs, S., Srinivas, M., Srinivasa, S.M., P, A., Prasad, M.N.N., and Rosell, R. (2025). Repurposing risperidone as an anti-angiogenic agent for triple-negative breast cancer: A computational to in ovo investigation. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1645905"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10147-024-02663-4","article-title":"Clinical benefits of adding olanzapine to 5-HT(3) receptor antagonist, NK(1) receptor antagonist, and dexamethasone for the prevention of nausea and vomiting in highly emetogenic chemotherapy: A systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023 from the Japan Society of Clinical Oncology","volume":"30","author":"Murakami","year":"2025","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1056\/NEJMoa1515725","article-title":"Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting","volume":"375","author":"Navari","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1667\/RADE-25-00222.1","article-title":"Repurposing Quetiapine as an Adjuvant Therapeutic Agent for Triple-Negative Breast Cancer","volume":"206","author":"He","year":"2026","journal-title":"Radiat. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/tox.23380","article-title":"The inhibitory effect and mechanism of quetiapine on tumor progression in hepatocellular carcinoma in vivo","volume":"37","author":"Su","year":"2022","journal-title":"Environ. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.21873\/anticanres.15237","article-title":"Lurasidone Sensitizes Cancer Cells to Osimertinib by Inducing Autophagy and Reduction of Survivin","volume":"41","author":"Suzuki","year":"2021","journal-title":"Anticancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/mdc3.12812","article-title":"Lurasidone-Induced Tardive Syndrome","volume":"6","author":"Tripathi","year":"2019","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ramachandran, S., Kaushik, I.S., and Srivastava, S.K. (2021). Pimavanserin: A Novel Autophagy Modulator for Pancreatic Cancer Treatment. Cancers, 13.","DOI":"10.3390\/cancers13225661"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.4081\/cp.2018.1044","article-title":"Neuroleptic malignant syndrome: A case responding to electroconvulsive therapy plus bupropion","volume":"8","year":"2018","journal-title":"Clin. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.18632\/oncotarget.26949","article-title":"In vitro and in vivo anti-tumor effects of brexpiprazole, a newly-developed serotonin-dopamine activity modulator with an improved safety profile","volume":"10","author":"Suzuki","year":"2019","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, X., He, J., Ma, A., Xia, W., Xia, Z., Liu, L., Wu, Z., and Chen, W. (2025). Brexpiprazole inhibits EMT and migration of colorectal cancer cells by downregulating the SREBP1\/SNAI1 signaling pathway. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1734678"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.21873\/anticanres.11085","article-title":"Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance","volume":"36","author":"Suzuki","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hussein, N., Ashby, C.R., Amawi, H., Nyinawabera, A., Vij, A., Khare, V.M., Karthikeyan, C., and Tiwari, A.K. (2018). Cariprazine, A Dopamine D(2)\/D(3) Receptor Partial Agonist, Modulates ABCG2-Mediated Multidrug Resistance in Cancer. Cancers, 10.","DOI":"10.3390\/cancers10090308"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mitrovic, M., Markovic, B.S., Rosic, G., Ristic, M., Jovicic, N., Jurisic, V., Milosavljevic, J., Matic, S., Ljujic, B., and Selakovic, D. (2026). Antipsychotic Drug Cariprazine Induces Distinct Cell Death Mechanisms in HeLa and HCT116 Cells as a Potential Inhibitor of Qi-Site of Cytochrome bc1 Reductase. Biomedicines, 14.","DOI":"10.3390\/biomedicines14020315"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhang, H., Liu, H., Xu, J., Li, X., Li, S., Liu, X., and Hu, C. (2026). From Antipsychotic to Antitumor Agent: Cariprazine Suppresses Glioblastoma via D2\/D3-ARRB2 Axis Modulation. Pharmaceuticals, 19.","DOI":"10.3390\/ph19060928"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15753","DOI":"10.1038\/s41598-018-33740-0","article-title":"Antiproliferative activities of the second-generation antipsychotic drug sertindole against breast cancers with a potential application for treatment of breast-to-brain metastases","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.18632\/oncotarget.2063","article-title":"Thioridazine inhibits angiogenesis and tumor growth by targeting the VEGFR-2\/PI3K\/mTOR pathway in ovarian cancer xenografts","volume":"5","author":"Park","year":"2014","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.2174\/1570163820666230606113158","article-title":"Repurposing Antipsychotic Agents Against Targets of Angiogenesis Pathways for Cancer Therapy: An in-silico Approach","volume":"20","author":"Kanmodi","year":"2023","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"34889","DOI":"10.18632\/oncotarget.26175","article-title":"The anti-psychotic drug pimozide is a novel chemotherapeutic for breast cancer","volume":"9","author":"Dakir","year":"2018","journal-title":"Oncotarget"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.cell.2012.03.049","article-title":"Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells","volume":"149","author":"Sachlos","year":"2012","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3892\/ol.2022.13302","article-title":"Perphenazine and prochlorperazine decrease glioblastoma U-87 MG cell migration and invasion: Analysis of the ABCB1 and ABCG2 transporters, E-cadherin, alpha-tubulin and integrins (alpha3, alpha5, and beta1) levels","volume":"23","author":"Otreba","year":"2022","journal-title":"Oncol. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/ijc.23562","article-title":"Reduced tumor growth in a mouse model of schizophrenia, lacking the dopamine transporter","volume":"123","author":"Asada","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Porta, C., Paglino, C., and Mosca, A. (2014). Targeting PI3K\/Akt\/mTOR Signaling in Cancer. Front. Oncol., 4.","DOI":"10.3389\/fonc.2014.00064"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12967-021-03209-2","article-title":"From GWAS to drug screening: Repurposing antipsychotics for glioblastoma","volume":"20","author":"Lin","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.cell.2017.05.016","article-title":"Wnt\/beta-Catenin Signaling, Disease, and Emerging Therapeutic Modalities","volume":"169","author":"Nusse","year":"2017","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Chu, C.W., Ko, H.J., Chou, C.H., Cheng, T.S., Cheng, H.W., Liang, Y.H., Lai, Y.L., Lin, C.Y., Wang, C., and Loh, J.K. (2019). Thioridazine Enhances P62-Mediated Autophagy and Apoptosis Through Wnt\/beta-Catenin Signaling Pathway in Glioma Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030473"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"116075","DOI":"10.1016\/j.bcp.2024.116075","article-title":"Targeting autophagy by antipsychotic phenothiazines: Potential drug repurposing for cancer therapy","volume":"222","author":"Lopes","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/jat.4397","article-title":"The role of phenothiazine derivatives in autophagy regulation: A systematic review","volume":"43","author":"Otreba","year":"2023","journal-title":"J. Appl. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wang, Z., Mi, T., Bradley, H.L., Metts, J., Sabnis, H., Zhu, W., Arbiser, J., and Bunting, K.D. (2021). Pimozide and Imipramine Blue Exploit Mitochondrial Vulnerabilities and Reactive Oxygen Species to Cooperatively Target High Risk Acute Myeloid Leukemia. Antioxidants, 10.","DOI":"10.3390\/antiox10060956"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"37568","DOI":"10.18632\/oncotarget.17247","article-title":"Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit","volume":"8","author":"Oliva","year":"2017","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"153528","DOI":"10.1016\/j.tox.2023.153528","article-title":"Phenothiazine derivatives and their impact on the necroptosis and necrosis processes. A review","volume":"492","author":"Otreba","year":"2023","journal-title":"Toxicology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"179012","DOI":"10.1016\/j.ejphar.2026.179012","article-title":"Trifluoperazine induces ferroptosis in acute myeloid leukemia by suppressing the Nrf2\/SLC7A11\/GPX4 axis","volume":"1029","author":"Xu","year":"2026","journal-title":"Eur. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"26948","DOI":"10.1038\/s41598-025-12645-9","article-title":"Haloperidol drug repurposing unveils ferroptosis involvement in breast cancer cells","volume":"15","author":"Consoli","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_61","first-page":"5399","article-title":"Inhibition of human breast cancer cell proliferation in tissue culture by the neuroleptic agents pimozide and thioridazine","volume":"50","author":"Strobl","year":"1990","journal-title":"Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ygyno.2010.10.003","article-title":"A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3\u2032-kinase (PI3K)\/AKT pathway in ovarian cancer cells","volume":"120","author":"Rho","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"496","DOI":"10.2174\/0115680096303479240614061136","article-title":"Revealing New Prospects: Antipsychotic Drugs Induces Anti-tumor Effects against Gastric Cancer through Inducing Apoptosis","volume":"25","author":"Amjadi","year":"2025","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1186\/s12967-024-05501-3","article-title":"Chlorpromazine overcomes temozolomide resistance in glioblastoma by inhibiting Cx43 and essential DNA repair pathways","volume":"22","author":"Matarrese","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"85997","DOI":"10.18632\/oncotarget.20844","article-title":"STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer","volume":"8","author":"Mohanty","year":"2017","journal-title":"Oncotarget"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.suponc.2011.05.002","article-title":"Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: A randomized phase III trial","volume":"9","author":"Navari","year":"2011","journal-title":"J. Support. Oncol."},{"key":"ref_67","first-page":"6177","article-title":"Olanzapine, an Atypical Antipsychotic, Inhibits Survivin Expression and Sensitizes Cancer Cells to Chemotherapeutic Agents","volume":"37","author":"Sanomachi","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1093\/schbul\/sbs065","article-title":"Incidence of cancer in patients with schizophrenia and their first-degree relatives: A population-based study in Sweden","volume":"39","author":"Ji","year":"2013","journal-title":"Schizophr. Bull."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/wps.20699","article-title":"20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20)","volume":"19","author":"Taipale","year":"2020","journal-title":"World Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1182\/bloodadvances.2018015677","article-title":"A phase 1 trial evaluating thioridazine in combination with cytarabine in patients with acute myeloid leukemia","volume":"2","author":"Aslostovar","year":"2018","journal-title":"Blood Adv."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Pace, A., Lombardi, G., Villani, V., Benincasa, D., Abbruzzese, C., Cestonaro, I., Corra, M., Padovan, M., Cerretti, G., and Caccese, M. (2023). Efficacy and safety of chlorpromazine as an adjuvant therapy for glioblastoma in patients with unmethylated MGMT gene promoter: RACTAC, a phase II multicenter trial. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1320710"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Hou, P.H., Chang, G.R., Chao, Y.T., Chang, Y.T., Hou, D.H., and Huang, S.S. (2025). Aripiprazole use and lowering the risk of breast cancer in patient with schizophrenia in a national cohort study. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0324257"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"178683","DOI":"10.1016\/j.ejphar.2026.178683","article-title":"From neuropsychiatric use to oncology: Repurposing antipsychotic drugs for cancer treatment","volume":"1019","author":"Ghaisas","year":"2026","journal-title":"Eur. J. Pharmacol."},{"key":"ref_74","first-page":"617","article-title":"Adverse effects of antipsychotic medications","volume":"81","author":"Muench","year":"2010","journal-title":"Am. Fam. Physician"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/cpt.1211","article-title":"Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle","volume":"106","author":"Bartelink","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"105454","DOI":"10.1016\/j.neubiorev.2023.105454","article-title":"An umbrella review of adverse effects associated with antipsychotic medications: The need for complementary study designs","volume":"155","author":"Chow","year":"2023","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Hao, J., Liu, H., Ye, Y., Lv, J., Xue, F., and Cai, Y. (2026). Network-driven prioritization and functional phenotyping nominate TTC23 as a biomarker-informed target in chlorpromazine repurposing for glioblastoma. Front. Pharmacol., 17.","DOI":"10.3389\/fphar.2026.1797067"},{"key":"ref_78","first-page":"475","article-title":"Mental Comorbidity and Psychosocial Care in Patients with Cancer","volume":"122","author":"Dinkel","year":"2025","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Waszkiewicz, N. (2025). The Future of Oncology in Psychiatric Medications. J. Clin. Med., 14.","DOI":"10.3390\/jcm14176003"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/14737140.2022.1987221","article-title":"Repurposing antipsychotic drugs for cancer treatment: Current evidence and future perspectives","volume":"22","author":"Lianos","year":"2022","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.3892\/ol.2016.4074","article-title":"Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges","volume":"11","author":"Lee","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lampros, M., Vlachos, N., Lianos, G.D., Bali, C., and Alexiou, G.A. (2025). Editorial: Drug repurposing for cancer treatment: Current and future directions. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1550672"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Gao, Z., Xi, Y., Shi, H., Ni, J., Xu, W., and Zhang, K. (2022). Antipsychotic exposure is an independent risk factor for breast cancer: A systematic review of epidemiological evidence. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.993367"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Hicks, B.M., Busby, J., Mills, K., O\u2019Neil, F.A., McIntosh, S.A., Zhang, S.D., Liberante, F.G., and Cardwell, C.R. (2020). Post-diagnostic antipsychotic use and cancer mortality: A population based cohort study. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07320-3"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/S0140-6736(00)02035-3","article-title":"QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients","volume":"355","author":"Reilly","year":"2000","journal-title":"Lancet"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/01.jcp.0000104913.75206.62","article-title":"A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition","volume":"24","author":"Harrigan","year":"2004","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_87","first-page":"1","article-title":"Antipsychotics and the Risks of Sudden Cardiac Death and All-Cause Death: Cohort Studies in Medicaid and Dually-Eligible Medicaid-Medicare Beneficiaries of Five States","volume":"1","author":"Leonard","year":"2013","journal-title":"J. Clin. Exp. Cardiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1017\/S1092852925100576","article-title":"Clozapine and anti-cancer agents: A systematic literature review of case reports","volume":"30","author":"Honor","year":"2025","journal-title":"CNS Spectr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e238377","DOI":"10.1136\/bcr-2020-238377","article-title":"Clozapine and chemotherapy: A dangerous couple or a necessary partnership?","volume":"13","author":"Campbell","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.schres.2026.04.016","article-title":"Risk and management of cancer in clozapine users: A systematic review","volume":"294","author":"Verdoux","year":"2026","journal-title":"Schizophr. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11920-026-01696-y","article-title":"Antipsychotics and Seizure Risk in Patients with Brain Tumors: Mechanisms, Modifiers, and Clinical Insights","volume":"28","author":"Taj","year":"2026","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1177\/10398562231158925","article-title":"Association between long-term use of prolactin-elevating antipsychotics in women and the risk of breast cancer: What are the clinical implications?","volume":"31","author":"Hope","year":"2023","journal-title":"Australas. Psychiatry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S2215-0366(25)00338-4","article-title":"Dose-dependent pharmacological mechanisms within the Neuroscience-based Nomenclature: A new concept to facilitate neuroscience-based prescribing","volume":"13","author":"Zemach","year":"2026","journal-title":"Lancet Psychiatry"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"pyag022","DOI":"10.1093\/ijnp\/pyag022","article-title":"Heterogeneity in adverse events associated with lumateperone: A study on potential subgroup-specific differences","volume":"29","author":"Jiang","year":"2026","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1080\/15384047.2020.1726718","article-title":"Phosphorylated STAT3 (Tyr705) as a biomarker of response to pimozide treatment in triple-negative breast cancer","volume":"21","author":"Dees","year":"2020","journal-title":"Cancer Biol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"882","DOI":"10.18632\/oncotarget.1801","article-title":"Genome-wide shRNA screen revealed integrated mitogenic signaling between dopamine receptor D2 (DRD2) and epidermal growth factor receptor (EGFR) in glioblastoma","volume":"5","author":"Li","year":"2014","journal-title":"Oncotarget"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"15330338211027913","DOI":"10.1177\/15330338211027913","article-title":"Dopamine Receptors in Cancer: Are They Valid Therapeutic Targets?","volume":"20","author":"Velazquez","year":"2021","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Ranjan, A., Kaushik, I., and Srivastava, S.K. (2020). Pimozide Suppresses the Growth of Brain Tumors by Targeting STAT3-Mediated Autophagy. Cells, 9.","DOI":"10.3390\/cells9092141"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"S458","DOI":"10.4103\/indianjpsychiatry.indianjpsychiatry_15_22","article-title":"Management of psychiatric disorders in patients with cancer","volume":"64","author":"Venkataramu","year":"2022","journal-title":"Indian J. Psychiatry"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrd.2018.92","article-title":"Overcoming the legal and regulatory barriers to drug repurposing","volume":"18","author":"Breckenridge","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Garcia-Diaz, M., Epstein, D., and Espin, J. (2025). Overcoming barriers to off-patent drug repurposing: A lifecycle-based policy solutions. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1670845"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrd1468","article-title":"Drug repositioning: Identifying and developing new uses for existing drugs","volume":"3","author":"Ashburn","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"27138","DOI":"10.1038\/s41598-024-78698-4","article-title":"Effects of antipsychotic drugs during radiotherapy in breast cancer in South Korea: A retrospective cohort study","volume":"14","author":"Hwang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-clinpsy-032813-153657","article-title":"Excess early mortality in schizophrenia","volume":"10","author":"Laursen","year":"2014","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1093\/schbul\/sbr148","article-title":"Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders\u2014A systematic review and meta-analysis","volume":"39","author":"Mitchell","year":"2013","journal-title":"Schizophr. Bull."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41537-023-00356-x","article-title":"Influencing factors of medication adherence in schizophrenic patients: A meta-analysis","volume":"9","author":"Guo","year":"2023","journal-title":"Schizophrenia"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e2447137","DOI":"10.1001\/jamanetworkopen.2024.47137","article-title":"Medication Exposure and Mortality in Patients With Schizophrenia","volume":"7","author":"Brodeur","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s13014-024-02558-8","article-title":"Use of antipsychotic drugs during radiotherapy in adult cancer patients in Korea: A nationwide retrospective cohort study based on the national health insurance service database","volume":"19","author":"Hwang","year":"2024","journal-title":"Radiat. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"26165","DOI":"10.1038\/srep26165","article-title":"Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis","volume":"6","author":"Ranjan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Moura, C., and Vale, N. (2023). The Role of Dopamine in Repurposing Drugs for Oncology. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071917"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s13045-020-00990-3","article-title":"Targeting the Wnt\/beta-catenin signaling pathway in cancer","volume":"13","author":"Zhang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"172402","DOI":"10.1016\/j.ejphar.2019.05.031","article-title":"Molecular mechanisms of anti-psychotic drugs for improvement of cancer treatment","volume":"856","author":"Hendouei","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Otreba, M., Sjolander, J.J., Grotli, M., and Sunnerhagen, P. (2021). A Small Molecule Targeting Human MEK1\/2 Enhances ERK and p38 Phosphorylation under Oxidative Stress or with Phenothiazines. Life, 11.","DOI":"10.3390\/life11040297"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-025-02180-4","article-title":"Targeting PI3K inhibitor resistance in breast cancer with metabolic drugs","volume":"10","author":"Gremke","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41392-020-0150-x","article-title":"DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer","volume":"5","author":"Huang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41537-025-00695-x","article-title":"Helping people to discontinue antipsychotics: If, when and how","volume":"11","author":"Moncrieff","year":"2025","journal-title":"Schizophrenia"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"107086","DOI":"10.1016\/j.phrs.2024.107086","article-title":"Biologics, theranostics, and personalized medicine in drug delivery systems","volume":"201","author":"Puccetti","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/ijc.70429","article-title":"Drug repurposing in oncology: Bridging computational discovery to clinical application","volume":"159","author":"Baskar","year":"2026","journal-title":"Int. J. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41563-019-0338-z","article-title":"Exploiting machine learning for end-to-end drug discovery and development","volume":"18","author":"Ekins","year":"2019","journal-title":"Nat. Mater."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10238-025-01965-9","article-title":"AI-driven multi-omics integration in precision oncology: Bridging the data deluge to clinical decisions","volume":"26","author":"Hsu","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev-med-050224-122802","article-title":"Artificial Intelligence to Guide Repurposing of Drugs","volume":"77","author":"Fu","year":"2026","journal-title":"Annu. Rev. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1124\/pharmrev.122.000810","article-title":"Pharmacogenomics: Driving Personalized Medicine","volume":"75","author":"Sadee","year":"2023","journal-title":"Pharmacol. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S2215-0366(19)30416-X","article-title":"Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: A systematic review and network meta-analysis","volume":"7","author":"Pillinger","year":"2020","journal-title":"Lancet Psychiatry"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:22:08Z","timestamp":1789705328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":123,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18182992"],"URL":"https:\/\/doi.org\/10.3390\/cancers18182992","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}