{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:29:09Z","timestamp":1762342149952,"version":"build-2065373602"},"reference-count":94,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T00:00:00Z","timestamp":1692489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Drug repositioning (DR) is the process of identifying novel therapeutic potentials for already-approved drugs and discovering new therapies for untreated diseases. DR can play an important role in optimizing the pre-clinical process of developing novel drugs by saving time and cost compared with the process of de novo drug discovery. Although the number of publications related to DR has rapidly increased, most therapeutic approaches were reported for malignant tumors. Surgical resection represents the definitive treatment for benign tumors of the central nervous system (BTCNS). However, treatment options remain limited for surgery-, chemotherapy- and radiation-refractory BTCNS, as well as malignant tumors. Meningioma, pituitary neuroendocrine tumor (PitNET), and schwannoma are the most common BTCNS. The treatment strategy using DR may be applied for refractory BTCNS, such as Grade 2 meningiomas, neurofibromatosis type 2-related schwannomatosis, and PitNETs with cavernous sinus invasion. In the setting of BTCNS, stable disease can provide significant benefit to the patient. DR may provide a longer duration of survival without disease progression for patients with refractory BTCNS. This article reviews the utility of DR for refractory BTCNS.<\/jats:p>","DOI":"10.3390\/ijms241612997","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T01:33:11Z","timestamp":1692581591000},"page":"12997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Drug Repositioning for Refractory Benign Tumors of the Central Nervous System"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8637-901X","authenticated-orcid":false,"given":"Ryota","family":"Tamura","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/jphp.13273","article-title":"Drug repositioning: A brief overview","volume":"72","author":"Jourdan","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd3078","article-title":"How to improve R&D productivity: The pharmaceutical industry\u2019s grand challenge","volume":"9","author":"Paul","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/nbt.2786","article-title":"Clinical development success rates for investigational drugs","volume":"32","author":"Hay","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/534314a","article-title":"Can you teach old drugs new tricks?","volume":"534","author":"Nosengo","year":"2016","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1758-2946-5-30","article-title":"Drug repositioning: A machine-learning approach through data integration","volume":"5","author":"Napolitano","year":"2013","journal-title":"J. Cheminform."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.semcancer.2019.09.012","article-title":"Drug repurposing for breast cancer therapy: Old weapon for new battle","volume":"68","author":"Aggarwal","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/cas.14318","article-title":"Drug repositioning in cancer: The current situation in Japan","volume":"111","author":"Masuda","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41392-020-00213-8","article-title":"Overcoming cancer therapeutic bottleneck by drug repurposing","volume":"5","author":"Zhang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1093\/neuonc\/nou283","article-title":"The worldwide incidence and prevalence of primary brain tumors: A systematic review and meta-analysis","volume":"17","author":"Fiest","year":"2015","journal-title":"Neuro-Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3322\/caac.21693","article-title":"Brain and other central nervous system tumor statistics, 2021","volume":"71","author":"Miller","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"492","DOI":"10.2176\/nmc.oa.2020-0438","article-title":"Epidemiologic Study of Primary Brain Tumors in Miyazaki Prefecture: A Regional 10-year Survey in Southern Japan","volume":"61","author":"Matsumoto","year":"2021","journal-title":"Neurol. Med.-Chir."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40001-023-01011-y","article-title":"The global prevalence of primary central nervous system tumors: A systematic review and meta-analysis","volume":"28","author":"Salari","year":"2023","journal-title":"Eur J Med Res"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ogasawara, C., Philbrick, B.D., and Adamson, D.C. (2021). Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030319"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"565582","DOI":"10.3389\/fonc.2020.565582","article-title":"Review of Atypical and Anaplastic Meningiomas: Classification, Molecular Biology, and Management","volume":"10","author":"Wilson","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1007\/s10143-022-01806-3","article-title":"Radiation therapy for atypical and anaplastic meningiomas: An overview of current results and controversial issues","volume":"45","author":"Vagnoni","year":"2022","journal-title":"Neurosurg. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tamura, R. (2021). Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115850"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3171\/2016.9.JNS161463","article-title":"Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: A matched cohort study with sporadic vestibular schwannomas","volume":"128","author":"Kruyt","year":"2018","journal-title":"J. Neurosurg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1200\/JCO.19.01367","article-title":"Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients with Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma","volume":"37","author":"Plotkin","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1093\/neuonc\/noad066","article-title":"Multicenter, prospective, phase 2 study of maintenance bevacizumab for children and adults with NF2-related schwannomatosis and progressive vestibular schwannoma","volume":"25","author":"Plotkin","year":"2023","journal-title":"Neuro-Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s10014-017-0284-x","article-title":"Bevacizumab for malignant gliomas: Current indications, mechanisms of action and resistance, and markers of response","volume":"34","author":"Tamura","year":"2017","journal-title":"Brain Tumor Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Trouillas, J., Jaffrain-Rea, M.L., Vasiljevic, A., Raverot, G., Roncaroli, F., and Villa, C. (2020). How to Classify the Pituitary Neuroendocrine Tumors (PitNET)s in 2020. Cancers, 12.","DOI":"10.3390\/cancers12020514"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/cen.14197","article-title":"A practical algorithm to predict postsurgical recurrence and progression of pituitary neuroendocrine tumours (PitNET)s","volume":"93","author":"Guaraldi","year":"2020","journal-title":"Clin. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"C5","DOI":"10.1530\/ERC-17-0004","article-title":"From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): An International Pituitary Pathology Club proposal","volume":"24","author":"Asa","year":"2017","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1038\/s41379-018-0110-y","article-title":"A common classification framework for neuroendocrine neoplasms: An International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal","volume":"31","author":"Rindi","year":"2018","journal-title":"Mod. Pathol."},{"key":"ref_26","first-page":"10","article-title":"Pituitary tumors. Introduction","volume":"Volume 8","author":"DeLellis","year":"2004","journal-title":"WHO Classification of Tumours, Pathology and Genetics of Tumours of Endocrine Organs"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s11060-014-1413-6","article-title":"Management of aggressive pituitary adenomas and pituitary carcinomas","volume":"117","author":"Heaney","year":"2014","journal-title":"J. Neuro-Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11154-019-09531-x","article-title":"Definition and diagnosis of aggressive pituitary tumors","volume":"21","author":"Kasuki","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s12022-019-9573-8","article-title":"PITX2 Expression in Non-functional Pituitary Neuroendocrine Tumor with Cavernous Sinus Invasion","volume":"30","author":"Tamura","year":"2019","journal-title":"Endocr. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/jhg.2017.91","article-title":"The pharmacogenomics of valproic acid","volume":"62","author":"Zhu","year":"2017","journal-title":"J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9959","DOI":"10.18632\/oncotarget.3692","article-title":"Valproic acid promotes radiosensitization in meningioma stem-like cells","volume":"6","author":"Chiou","year":"2015","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/BF00558451","article-title":"Plasma concentrations of mebendazole during treatment of echinococcosis: Preliminary results","volume":"17","author":"Karlaganis","year":"1980","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Guerini, A.E., Triggiani, L., Maddalo, M., Bon\u00f9, M.L., Frassine, F., Baiguini, A., Alghisi, A., Tomasini, D., Borghetti, P., and Pasinetti, N. (2019). Mebendazole as a candidate for drug repurposing in oncology: An extensive review of current literature. Cancers, 11.","DOI":"10.3390\/cancers11091284"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/1535-7163.MCT-14-0755-T","article-title":"Repurposing the antihelmintic mebendazole as a hedgehog inhibitor","volume":"14","author":"Larsen","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1093\/neuonc\/nou234","article-title":"Effective treatment of diverse medulloblastoma models with mebendazole and its impact on tumor angiogenesis","volume":"17","author":"Bai","year":"2015","journal-title":"Neuro-Oncol."},{"key":"ref_36","first-page":"1201","article-title":"The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells","volume":"1","author":"Sasaki","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s11060-018-03009-7","article-title":"Mebendazole and radiation in combination increase survival through anticancer mechanisms in an intracranial rodent model of malignant meningioma","volume":"140","author":"Skibinski","year":"2018","journal-title":"J. Neuro-Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s41574-019-0242-2","article-title":"Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus","volume":"15","author":"Foretz","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_39","first-page":"59","article-title":"Metformin may function as anti-cancer agent via targeting cancer stem cells: The potential biological significance of tumor-associated miRNAs in breast and pancreatic cancers","volume":"2","author":"Bao","year":"2014","journal-title":"Ann. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/abbs\/gmx106","article-title":"Metformin as an anti-cancer agent: Actions and mechanisms targeting cancer stem cells","volume":"50","author":"Saini","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1007\/s00125-013-2991-0","article-title":"Molecular mechanism of action of metformin: Old or new insights?","volume":"56","author":"Rena","year":"2013","journal-title":"Diabetologia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.omto.2020.11.004","article-title":"Metformin enhances anti-cancer effects of cisplatin in meningioma through AMPK-mTOR signaling pathways","volume":"20","author":"Guo","year":"2020","journal-title":"Mol. Ther. Oncolytics."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7507","DOI":"10.1158\/0008-5472.CAN-09-2994","article-title":"Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission","volume":"69","author":"Hirsch","year":"2009","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.lfs.2018.05.046","article-title":"Metformin enhances cisplatin induced inhibition of cholangiocarcinoma cells via AMPK-mTOR pathway","volume":"207","author":"Wandee","year":"2018","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fsurg.2019.00023","article-title":"Expression of components of the renin-angiotensin system by the putative stem cell population within WHO grade I meningioma","volume":"6","author":"Shivapathasundram","year":"2019","journal-title":"Front. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3171\/2016.9.JNS16431","article-title":"(Pro)renin receptor is crucial for glioma development via the Wnt\/\u03b2-catenin signaling pathway","volume":"127","author":"Masaaki","year":"2017","journal-title":"J. Neurosurg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/bs.acr.2020.05.003","article-title":"Ca(2+) as a therapeutic target in cancer","volume":"148","author":"Gross","year":"2020","journal-title":"Adv. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3389\/fonc.2019.00745","article-title":"Therapeutic targeting of cancer stem cells via modulation of the renin-angiotensin system","volume":"9","author":"Roth","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Antal, L., and Martin-Caraballo, M. (2019). T-type calcium channels in cancer. Cancers, 11.","DOI":"10.3390\/cancers11020134"},{"key":"ref_50","first-page":"1435","article-title":"Novel insights into ion channels in cancer stem cells","volume":"53","author":"Cheng","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1227\/00006123-199502000-00017","article-title":"In vitro growth inhibition of growth factor-stimulated meningioma cells by calcium channel antagonists","volume":"36","author":"Jensen","year":"1995","journal-title":"Neurosurgery"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1227\/00006123-199511000-00013","article-title":"Inhibition of in vitro meningioma proliferation after growth factor stimulation by calcium channel antagonists: Part II\u2014Additional growth factors, growth factor receptor immunohistochemistry, and intracellular calcium measurements","volume":"37","author":"Jensen","year":"1995","journal-title":"Neurosurgery"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0090-3019(01)00444-X","article-title":"Calcium channel antagonists inhibit growth of subcutaneous xenograft meningiomas in nude mice","volume":"55","author":"Jensen","year":"2001","journal-title":"Surg. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"E10","DOI":"10.3171\/FOC-07\/10\/E10","article-title":"Chronic suppressive therapy with calcium channel antagonists for refractory meningiomas","volume":"23","author":"Ragel","year":"2007","journal-title":"Neurosurg. Focus"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1177\/107327480301000206","article-title":"New approaches for the treatment of refractory meningiomas","volume":"10","author":"Ragel","year":"2003","journal-title":"Cancer Control"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.wneu.2015.09.060","article-title":"Combined hydroxyurea and verapamil in the clinical treatment of refractory meningioma: Human and orthotopic xenograft studies","volume":"86","author":"Karsy","year":"2016","journal-title":"World Neurosurg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1023\/A:1014588214966","article-title":"Lovastatin is a potent inhibitor of meningioma cell proliferation: Evidence for inhibition of a mitogen associated protein kinase","volume":"56","author":"Johnson","year":"2002","journal-title":"J. Neuro-Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1227\/01.NEU.0000360130.52812.1D","article-title":"Effect of simvastatin on glioma cell proliferation, migration, and apoptosis","volume":"65","author":"Wu","year":"2009","journal-title":"Neurosurgery"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"725","DOI":"10.4103\/0973-1482.146127","article-title":"Investigation of simvastatin-induced apoptosis and cell cycle arrest in cancer stem cells of MCF-7","volume":"12","author":"Afzali","year":"2016","journal-title":"J. Cancer Res. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2014.12.007","article-title":"Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas","volume":"166","author":"Dilwali","year":"2015","journal-title":"Transl. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00281-012-0342-8","article-title":"Multifaceted roles of PGE2 in inflammation and cancer","volume":"35","author":"Nakanishi","year":"2013","journal-title":"Semin. Immunopathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/MAO.0000000000000189","article-title":"Aspirin intake correlates with halted growth of sporadic vestibular schwannoma in vivo","volume":"35","author":"Kandathil","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1158\/0008-5472.CAN-15-1144","article-title":"YAP mediates tumorigenesis in neurofibromatosis type 2 by promoting cell survival and proliferation through a COX-2-EGFR signaling axis","volume":"76","author":"Guerrant","year":"2016","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"718","DOI":"10.18632\/oncotarget.22002","article-title":"Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2","volume":"9","author":"Wahle","year":"2018","journal-title":"Oncotarget"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1002\/lary.27114","article-title":"Aspirin does not prevent growth of vestibular schwannomas: A case-control study","volume":"128","author":"MacKeith","year":"2018","journal-title":"Laryngoscope"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s40478-019-0760-0","article-title":"COX2 expression is associated with proliferation and tumor extension in vestibular schwannoma but is not influenced by acetylsalicylic acid intake","volume":"7","author":"Behling","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1097\/MAO.0000000000001506","article-title":"Vestibular schwannoma growth with aspirin and other nonsteroidal anti-inflammatory drugs","volume":"38","author":"Hunter","year":"2017","journal-title":"Otol. Neurotol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1096\/fj.00-0843fje","article-title":"Aspirin inhibits NF-kappa B and protects from angiotensin II-induced organ damage","volume":"15","author":"Muller","year":"2001","journal-title":"FASEB J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1093\/hmg\/ddy361","article-title":"A proteasome-resistant fragment of NIK mediates oncogenic NF-kappa B signaling in schwannomas","volume":"28","author":"Gehlhausen","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"E52","DOI":"10.1093\/neuros\/nyx516","article-title":"Congress of neurological surgeons systematic review and evidence-based guidelines on emerging therapies for the treatment of patients with vestibular schwannomas","volume":"82","author":"Agazzi","year":"2018","journal-title":"Neurosurgery"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5437","DOI":"10.1038\/s41598-018-23609-7","article-title":"Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma","volume":"8","author":"Sagers","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"E7766","DOI":"10.1073\/pnas.1702946114","article-title":"NLRP3 mutation and cochlear autoinflammation cause syndromic and nonsyndromic hearing loss DFNA34 responsive to anakinra therapy","volume":"114","author":"Nakanishi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"107770","DOI":"10.1016\/j.heares.2019.07.007","article-title":"NLRP3 inflammasome activation in human vestibular schwannoma: Implications for tumor-induced hearing loss","volume":"381","author":"Sagers","year":"2019","journal-title":"Hear. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e534","DOI":"10.1097\/MJT.0000000000001559","article-title":"Mifepristone: A Safe Method of Medical Abortion and Self-Managed Medical Abortion in the Post-Roe Era","volume":"29","author":"Schmidt","year":"2022","journal-title":"Am. J. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.molonc.2015.03.009","article-title":"Preclinical validation of anti-nuclear factor-kappa B therapy to inhibit human vestibular schwannoma growth","volume":"9","author":"Sonam","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3390\/endocrines1010006","article-title":"Recent Progress in Stem Cell Research of the Pituitary Gland and Pituitary Adenoma","volume":"1","author":"Toda","year":"2020","journal-title":"Endocrines"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.drudis.2012.06.001","article-title":"The status of the art of human malignant glioma management: The promising role of targeting tumor-initiating cells","volume":"17","author":"Florio","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/cbf.3661","article-title":"Metformin suppresses self-renewal and stemness of cancer stem cell models derived from pluripotent stem cells","volume":"39","author":"Zahra","year":"2021","journal-title":"Cell Biochem Funct"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"37538","DOI":"10.18632\/oncotarget.16556","article-title":"Metformin inhibits proliferation and growth hormone secretion of GH3 pituitary adenoma cells","volume":"8","author":"An","year":"2017","journal-title":"Oncotarget"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.drudis.2015.09.017","article-title":"Drug-repositioning opportunities for cancer therapy: Novel molecular targets for known compounds","volume":"21","author":"Wurth","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/s42003-022-04272-1","article-title":"Proteogenomic landscape and clinical characterization of GH-producing pituitary adenomas\/somatotroph pituitary neuroendocrine tumors","volume":"5","author":"Yamato","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1530\/ERC-14-0546","article-title":"Pituitary tumors contain a side population with tumor stem cell-associated characteristics","volume":"22","author":"Mertens","year":"2015","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/sj.bjc.6605142","article-title":"Isolation of tumour stem-like cells from benign tumours","volume":"101","author":"Xu","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3389\/fendo.2017.00339","article-title":"The stem cell connection of pituitary tumors","volume":"8","author":"Vankelecom","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.3892\/mmr.2015.3664","article-title":"Disulfiram sensitizes pituitary adenoma cells to temozolomide by regulating O6-methylguanine-DNA methyltransferase expression","volume":"12","author":"Zhao","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S1470-2045(14)71171-4","article-title":"Tamoxifen for prevention of breast cancer: Extended long-term follow-up of the IBIS-I breast cancer prevention trial","volume":"16","author":"Cuzick","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"899","DOI":"10.2217\/imt-2018-0006","article-title":"Dual role of macrophage in tumor immunity","volume":"10","author":"Tamura","year":"2018","journal-title":"Immunotherapy"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lv, T., Zhang, Z., Yu, H., Ren, S., Wang, J., Li, S., and Sun, L. (2022). Tamoxifen Exerts Anticancer Effects on Pituitary Adenoma Progression via Inducing Cell Apoptosis and Inhibiting Cell Migration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052664"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1060884","DOI":"10.3389\/fendo.2022.1060884","article-title":"Individualized medical treatment options in Cushing disease","volume":"13","author":"Rzepka","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41392-020-00284-7","article-title":"Bexarotene combined with lapatinib for the treatment of Cushing\u2019s disease: Evidence based on drug repositioning and experimental confirmation","volume":"5","author":"Yu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/1346-8138.15310","article-title":"Efficacy and safety of bexarotene combined with photo(chemo)therapy for cutaneous T-cell lymphoma","volume":"47","author":"Morita","year":"2020","journal-title":"J. Dermatol."},{"key":"ref_92","first-page":"CD004424","article-title":"Antiepileptic drugs for preventing seizures in people with brain tumors","volume":"2008","author":"Ratilal","year":"2008","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1089\/adt.2015.29011.tiodrrr","article-title":"Computational and practical aspects of drug repositioning","volume":"13","author":"Oprea","year":"2015","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1208\/s12248-012-9390-1","article-title":"Drug Repurposing: Far Beyond New Targets for Old Drugs","volume":"14","author":"Oprea","year":"2012","journal-title":"AAPS J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/16\/12997\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:38:02Z","timestamp":1760128682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/16\/12997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,20]]},"references-count":94,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241612997"],"URL":"https:\/\/doi.org\/10.3390\/ijms241612997","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,8,20]]}}}