{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T14:00:27Z","timestamp":1793023227399,"version":"4.5.0"},"reference-count":158,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Development of Diagnostics and Therapy in Warsaw"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Subependymal giant cell astrocytoma (SEGA) is most often found in patients with TSC (Tuberous Sclerosis Complex). Although it has been classified as a benign tumor, it may create a serious medical problem leading to grave consequences, including young patient demise. Surgery and chemotherapy belong to the gold standard of treatment. A broader pharmacological approach involves the ever-growing number of rapalogs and ATP-competitive inhibitors, as well as compounds targeting other kinases, such as dual PI3K\/mTOR inhibitors and CK2 kinase inhibitors. Novel approaches may utilize noncoding RNA-based therapeutics and are extensively investigated to this end. The purpose of our review was to characterize SEGA and discuss the latest trends in the diagnosis and therapy of this disease.<\/jats:p>","DOI":"10.3390\/cancers16193406","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T07:30:18Z","timestamp":1728286218000},"page":"3406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Subependymal Giant Cell Astrocytoma: The Molecular Landscape and Treatment Advances"],"prefix":"10.3390","volume":"16","author":[{"given":"Emanuela","family":"Pucko","sequence":"first","affiliation":[{"name":"Department of Neurooncology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 St., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1697-8164","authenticated-orcid":false,"given":"Dorota","family":"Sulejczak","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 St., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of Neurooncology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 St., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1440-1789.2008.00934.x","article-title":"Subependymal giant cell astrocytoma (SEGA): Is it an astrocytoma? Morphological, immunohistochemical and ultrastructural study","volume":"29","author":"Buccoliero","year":"2009","journal-title":"Neuropathology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.5414\/NP300936","article-title":"Subependymal giant cell astrocytoma: A lesion with activated mTOR pathway and constant expression of glutamine synthetase","volume":"35","author":"Buccoliero","year":"2016","journal-title":"Clin. Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.spen.2015.10.003","article-title":"Natural History and Current Treatment Options for Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis Complex","volume":"22","author":"Mandera","year":"2015","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_4","first-page":"139","article-title":"Brain lesions in tuberous sclerosis complex. Review","volume":"48","author":"Grajkowska","year":"2010","journal-title":"Folia Neuropathol."},{"key":"ref_5","first-page":"61","article-title":"Beyond Benign: A Case of Subependymal Giant Cell Astrocytomas Provoking Hydrocephalus in Tuberous Sclerosis Complex","volume":"31","year":"2024","journal-title":"Acta Med. Litu."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gao, C., Zabielska, B., Jiao, F., Mei, D., Wang, X., Kotulska, K., and Jozwiak, S. (2023). Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex-Current Views on Their Pathogenesis and Management. J. Clin. Med., 12.","DOI":"10.3390\/jcm12030956"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Jansen, A.C., Belousova, E., Benedik, M.P., Carter, T., Cottin, V., Curatolo, P., Dahlin, M., D\u2019Amato, L., d\u2019Aug\u00e8res, G.B., and de Vries, P.J. (2019). Clinical Characteristics of Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis Complex. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00705"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.17712\/nsj.2020.1.20190044","article-title":"Infantile atypical subependymal giant cell astrocytoma","volume":"25","author":"Almubarak","year":"2020","journal-title":"Neurosciences"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/neup.12948","article-title":"SEGA-like circumscribed astrocytoma in a non-NF1 patient, harboring molecular profile of GBM. A case report","volume":"44","author":"Yamada","year":"2024","journal-title":"Neuropathology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10334-017-0614-3","article-title":"What are the true volumes of SEGA tumors? Reliability of planimetric and popular semi-automated image segmentation methods","volume":"30","author":"Stawiski","year":"2017","journal-title":"Magma"},{"key":"ref_11","first-page":"e39187","article-title":"Subependymal Giant Cell Astrocytoma Non-Associated with Tuberous Sclerosis Complex and Expression of OCT-4 and INI-1: A Case Report","volume":"15","year":"2023","journal-title":"Cureus"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s13256-024-04649-2","article-title":"Radiotherapy for subependymal giant cell astrocytoma: Time to challenge a historical ban? A case report and review of the literature","volume":"18","author":"Kamel","year":"2024","journal-title":"J. Med. Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11940-021-00673-5","article-title":"Subependymal Giant Cell Astrocytomas (SEGAs): A Model of Targeting Tumor Growth and Epilepsy","volume":"23","author":"Mo","year":"2021","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1212\/01.WNL.0000158653.81008.49","article-title":"Developmental origin of subependymal giant cell astrocytoma in tuberous sclerosis complex","volume":"64","author":"Ess","year":"2005","journal-title":"Neurology"},{"key":"ref_15","first-page":"171","article-title":"Cytomorphology of subependymal giant cell astrocytoma","volume":"36","author":"Altermatt","year":"1992","journal-title":"Acta Cytol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/S0387-7604(01)00304-7","article-title":"Neuropathology of tuberous sclerosis","volume":"23","author":"Mizuguchi","year":"2001","journal-title":"Brain Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/BF00691851","article-title":"Subependymal giant cell astrocytoma. Significance and possible cytogenetic implications of an immunohistochemical study","volume":"62","author":"Bonnin","year":"1984","journal-title":"Acta Neuropathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/j.1346-8138.1992.tb03802.x","article-title":"The neuropathology of tuberous sclerosis","volume":"19","author":"Scheithauer","year":"1992","journal-title":"J. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s00381-008-0681-x","article-title":"Congenital subependymal giant cell astrocytoma: Clinical considerations and expression of radial glial cell markers in giant cells","volume":"24","author":"Phi","year":"2008","journal-title":"Childs Nerv. Syst."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1016\/j.wneu.2021.11.125","article-title":"TTF-1: A Well-Favored Addition to the Immunohistochemistry Armamentarium as a Diagnostic Marker of SEGA","volume":"159","author":"Dutta","year":"2022","journal-title":"World Neurosurg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/S1357-2725(97)00007-1","article-title":"Thyroid transcription factor-1","volume":"29","author":"Bingle","year":"1997","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1242\/dev.113.4.1093","article-title":"The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain","volume":"113","author":"Lazzaro","year":"1991","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1006\/mcne.2000.0933","article-title":"TTF-1, a Homeodomain Gene Required for Diencephalic Morphogenesis, Is Postnatally Expressed in the Neuroendocrine Brain in a Developmentally Regulated and Cell-Specific Fashion","volume":"17","author":"Lee","year":"2001","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/modpathol.2016.205","article-title":"Thyroid transcription factor-1 distinguishes subependymal giant cell astrocytoma from its mimics and supports its cell origin from the progenitor cells in the medial ganglionic eminence","volume":"30","author":"Hang","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00401-021-02377-1","article-title":"Genetic and epigenetic characterization of posterior pituitary tumors","volume":"142","author":"Schmid","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Feliciano, D.M. (2020). The Neurodevelopmental Pathogenesis of Tuberous Sclerosis Complex (TSC). Front. Neuroanat., 14.","DOI":"10.3389\/fnana.2020.00039"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95516","DOI":"10.18632\/oncotarget.20764","article-title":"Subependymal giant cell astrocytomas in Tuberous Sclerosis Complex have consistent TSC1\/TSC2 biallelic inactivation, and no BRAF mutations","volume":"8","author":"Bongaarts","year":"2017","journal-title":"Oncotarget"},{"key":"ref_28","unstructured":"WHO Classification of Tumours Editorial Board (2022). Central Nervous System Tumours: Who Classification of Tumours, WHO Classification of Tumours Editorial Board, IARC Publications. [5th ed.]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s00381-002-0700-2","article-title":"Subependymal giant cell astrocytoma in children with tuberous sclerosis","volume":"19","author":"Cuccia","year":"2003","journal-title":"Childs Nerv. Syst."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s41016-017-0077-4","article-title":"Clinical and imaging features of subependymal giant cell astrocytoma: Report of 20 cases","volume":"3","author":"Mei","year":"2017","journal-title":"Chin. Neurosurg. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5114\/fn.2015.49969","article-title":"Erk activation as a possible mechanism of transformation of subependymal nodule into subependymal giant cell astrocytoma","volume":"53","author":"Siedlecka","year":"2015","journal-title":"Folia Neuropathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.neuchi.2022.07.003","article-title":"Subependymal giant-cell astrocytoma: A surgical review in the modern era of mTOR inhibitors","volume":"68","author":"Danassegarane","year":"2022","journal-title":"Neurochirurgie"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1007\/s00018-012-1196-x","article-title":"mTOR signaling in neural stem cells: From basic biology to disease","volume":"70","author":"Magri","year":"2013","journal-title":"Cell Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fogarasi, A., De Waele, L., Bartalini, G., Jozwiak, S., Laforgia, N., Verhelst, H., Petrak, B., Pedespan, J.M., Witt, O., and Castellana, R. (2016). EFFECTS: An expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex. BMC Neurol., 16.","DOI":"10.1186\/s12883-016-0658-4"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","article-title":"Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference","volume":"49","author":"Northrup","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.pediatrneurol.2013.08.017","article-title":"Subependymal giant cell astrocytoma: Diagnosis, screening, and treatment. Recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012","volume":"49","author":"Roth","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1002\/pbc.25573","article-title":"Dose-level response rates of mTor inhibition in tuberous sclerosis complex (TSC) related subependymal giant cell astrocytoma (SEGA)","volume":"62","author":"Weidman","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/pbc.25964","article-title":"Mammalian Target of Rapamycin Inhibitor Induced Complete Remission of a Recurrent Subependymal Giant Cell Astrocytoma in a Patient without Features of Tuberous Sclerosis Complex","volume":"63","author":"Appalla","year":"2016","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1007\/s00381-020-04823-z","article-title":"A case of subependymal giant cell astrocytoma without tuberous sclerosis complex and review of the literature","volume":"37","author":"Chandran","year":"2021","journal-title":"Childs Nerv. Syst."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13256-016-0818-6","article-title":"Subependymal giant cell astrocytoma (SEGA): A case report and review of the literature","volume":"10","author":"Lamchahab","year":"2016","journal-title":"J. Med. Case Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00381-023-06105-w","article-title":"Isolated subependymal giant cell astrocytoma (SEGA) in the absence of clinical tuberous sclerosis: Two case reports and literature review","volume":"40","author":"Cobourn","year":"2024","journal-title":"Childs Nerv. Syst."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3171\/jns.1979.50.1.0106","article-title":"Recurrent subependymal giant-cell astrocytoma in the absence of tuberous sclerosis. Case report","volume":"50","author":"Halmagyi","year":"1979","journal-title":"J. Neurosurg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jocn.2020.10.017","article-title":"Solitary subependymal giant cell astrocytoma: Case report and review of the literature","volume":"82","author":"Corlette","year":"2020","journal-title":"J. Clin. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1007\/s00381-020-04839-5","article-title":"A case of solitary subependymal giant cell astrocytoma with histopathological anaplasia and TSC2 gene alteration","volume":"37","author":"Suzuki","year":"2021","journal-title":"Childs Nerv. Syst."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1007\/s00467-014-3027-9","article-title":"Tuberous sclerosis complex: The past and the future","volume":"30","author":"Lagae","year":"2015","journal-title":"Pediatr. Nephrol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1086\/316951","article-title":"Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs","volume":"68","author":"Dabora","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Man, A., Di Scipio, M., Grewal, S., Suk, Y., Trinari, E., Ejaz, R., and Whitney, R. (2024). The Genetics of Tuberous Sclerosis Complex and Related mTORopathies: Current Understanding and Future Directions. Genes, 15.","DOI":"10.3390\/genes15030332"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Avgeris, S., Fostira, F., Vagena, A., Ninios, Y., Delimitsou, A., Vodicka, R., Vrtel, R., Youroukos, S., Stravopodis, D.J., and Vlassi, M. (2017). Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-16988-w"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/TACG.S90262","article-title":"Genetics of tuberous sclerosis complex: Implications for clinical practice","volume":"10","author":"Caban","year":"2017","journal-title":"Appl. Clin. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1590\/1678-4685-gmb-2015-0321","article-title":"TSC1 and TSC2 gene mutations and their implications for treatment in Tuberous Sclerosis Complex: A review","volume":"40","author":"Rosset","year":"2017","journal-title":"Genet. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/sj.ejhg.5201402","article-title":"Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: Genotype\u2014Phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex","volume":"13","author":"Sancak","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1054\/jcms.2002.0322","article-title":"Tuberous sclerosis: Clinicopathologic features and review of the literature","volume":"30","author":"Barron","year":"2002","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMra055323","article-title":"The tuberous sclerosis complex","volume":"355","author":"Crino","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","article-title":"Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations","volume":"123","author":"Northrup","year":"2021","journal-title":"Pediatr. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s11916-022-01032-y","article-title":"Managing Headache Disorders Associated with Tuberous Sclerosis and Neurofibromatosis","volume":"26","author":"Patniyot","year":"2022","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Crainic, N., Furtner, J., Pallud, J., Bielle, F., Lombardi, G., Rud\u00e0, R., and Idbaih, A. (2023). Rare Neuronal, Glial and Glioneuronal Tumours in Adults. Cancers, 15.","DOI":"10.3390\/cancers15041120"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Gelot, A.B., and Represa, A. (2020). Progression of Fetal Brain Lesions in Tuberous Sclerosis Complex. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00899"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1824-7288-39-57","article-title":"Is mTOR inhibition a systemic treatment for tuberous sclerosis?","volume":"39","author":"Moavero","year":"2013","journal-title":"Ital. J. Pediatr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.pedhc.2006.05.004","article-title":"Tuberous sclerosis complex: A review","volume":"21","author":"Leung","year":"2007","journal-title":"J. Pediatr. Health Care"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"475","DOI":"10.2174\/138920208786241243","article-title":"Genetics and molecular biology of tuberous sclerosis complex","volume":"9","author":"Napolioni","year":"2008","journal-title":"Curr. Genom."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3171\/2015.1.PEDS13146","article-title":"Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex: Case report","volume":"16","author":"Beaumont","year":"2015","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00381-010-1222-y","article-title":"Regression of subependymal giant cell astrocytomas with RAD001 (Everolimus) in tuberous sclerosis complex","volume":"27","author":"Yalon","year":"2011","journal-title":"Child\u2019s Nerv. Syst."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6516","DOI":"10.1158\/0008-5472.CAN-07-6188","article-title":"S6K1 plays a key role in glial transformation","volume":"68","author":"Nakamura","year":"2008","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41392-023-01608-z","article-title":"Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease","volume":"8","author":"Panwar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Cui, D., Qu, R., Liu, D., Xiong, X., Liang, T., and Zhao, Y. (2021). The Cross Talk between p53 and mTOR Pathways in Response to Physiological and Genotoxic Stresses. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.775507"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1074\/jbc.M110.159046","article-title":"ERK1\/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1)","volume":"286","author":"Carriere","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1093\/hmg\/6.12.2155","article-title":"Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis","volume":"6","author":"Jones","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"708","DOI":"10.4103\/neurol-india.Neurol-India-D-23-00343","article-title":"The Clinicopathological Features of the Solitary Subependymal Giant Cell Astrocytoma: A Systematic Review","volume":"72","year":"2024","journal-title":"Neurol. India"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1038\/s41436-020-0823-4","article-title":"TSC2 pathogenic variants are predictive of severe clinical manifestations in TSC infants: Results of the EPISTOP study","volume":"22","author":"Hamieh","year":"2020","journal-title":"Genet. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1007\/s00381-014-2555-8","article-title":"Congenital subependymal giant cell astrocytomas in patients with tuberous sclerosis complex","volume":"30","author":"Kotulska","year":"2014","journal-title":"Child\u2019s Nerv. Syst."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/s41379-020-00659-9","article-title":"Subependymal giant cell astrocytomas are characterized by mTORC1 hyperactivation, a very low somatic mutation rate, and a unique gene expression profile","volume":"34","author":"Giannikou","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1038\/s41379-018-0103-x","article-title":"Subependymal giant cell astrocytoma-like astrocytoma: A neoplasm with a distinct phenotype and frequent neurofibromatosis type-1-association","volume":"31","author":"Palsgrove","year":"2018","journal-title":"Mod. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1007\/s00381-020-04551-4","article-title":"Identification of TSC1 or TSC2 mutation limited to the tumor in three cases of solitary subependymal giant cell astrocytoma using next-generation sequencing technology","volume":"36","author":"Fohlen","year":"2020","journal-title":"Childs Nerv. Syst."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00381-021-05399-y","article-title":"TSC2 somatic mosaic mutation, including extra-tumor tissue, may be the developmental cause of solitary subependymal giant cell astrocytoma","volume":"38","author":"Sasaki","year":"2022","journal-title":"Childs Nerv. Syst."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"988","DOI":"10.4103\/0028-3886.190274","article-title":"Role of mTOR signaling pathway in the pathogenesis of subependymal giant cell astrocytoma\u2014A study of 28 cases","volume":"64","author":"Kumari","year":"2016","journal-title":"Neurol. India"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Popova, N.V., and J\u00fccker, M. (2021). The Role of mTOR Signaling as a Therapeutic Target in Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041743"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1007\/s00381-024-06382-z","article-title":"Bleeding solitary SEGA in non-tuberous sclerosis complex adolescent: A case illustration and review of literature","volume":"40","author":"Yindeedej","year":"2024","journal-title":"Childs Nerv. Syst."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.pediatrneurol.2023.08.015","article-title":"Subependymal Giant Cell Astrocytoma Tumors in Patients without Clinical Manifestation of Tuberous Sclerosis Complex: A Diagnostic Puzzle","volume":"150","author":"Zabielska","year":"2024","journal-title":"Pediatr. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.pediatrneurol.2021.07.008","article-title":"TSC1 Mosaicism Leading to Subependymal Giant Cell Astrocytoma but Not Tuberous Sclerosis Complex","volume":"123","author":"Hall","year":"2021","journal-title":"Pediatr. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.ajhg.2023.04.002","article-title":"Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex","volume":"110","author":"Klonowska","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1080\/14656566.2020.1751124","article-title":"Pharmacological treatment strategies for subependymal giant cell astrocytoma (SEGA)","volume":"21","author":"Franz","year":"2020","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.2353\/ajpath.2010.090950","article-title":"Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex and new therapeutic implications","volume":"176","author":"Tyburczy","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.ejpn.2012.12.008","article-title":"Management of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC): Clinical recommendations","volume":"17","author":"Nabbout","year":"2013","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ajpath.2010.11.031","article-title":"Enhanced epidermal growth factor, hepatocyte growth factor, and vascular endothelial growth factor expression in tuberous sclerosis complex","volume":"178","author":"Parker","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ejpn.2012.10.005","article-title":"The outcome of surgical management of subependymal giant cell astrocytoma in tuberous sclerosis complex","volume":"17","author":"Amin","year":"2013","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/978-3-031-53578-9_5","article-title":"Pediatric-Like Brain Tumors in Adults","volume":"50","author":"Dias","year":"2024","journal-title":"Adv. Tech. Stand. Neurosurg."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2176\/jns-nmc.2022-0375","article-title":"Neoadjuvant Therapy with Everolimus for Subependymal Giant Cell Astrocytoma: A Case Report","volume":"10","author":"Karita","year":"2023","journal-title":"NMC Case Rep. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1056\/NEJMoa1001671","article-title":"Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis","volume":"363","author":"Krueger","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/cns3.20070","article-title":"Preventative treatment of tuberous sclerosis complex with sirolimus: Phase I safety and efficacy results","volume":"2","author":"Capal","year":"2024","journal-title":"Ann. Child Neurol. Soc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1185\/03007995.2012.658907","article-title":"Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: A national claims database analysis","volume":"28","author":"Sun","year":"2012","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1185\/03007995.2012.658908","article-title":"Surgical resection of subependymal giant cell astrocytomas (SEGAs) and changes in SEGA-related conditions: A US national claims database study","volume":"28","author":"Sun","year":"2012","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.pediatrneurol.2013.12.004","article-title":"Surgical treatment of subependymal giant cell astrocytoma in tuberous sclerosis complex patients","volume":"50","author":"Kotulska","year":"2014","journal-title":"Pediatr. Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"224","DOI":"10.2176\/nmc.42.224","article-title":"Rapid regrowth of solitary subependymal giant cell astrocytoma\u2014Case report","volume":"42","author":"Yamamoto","year":"2002","journal-title":"Neurol. Med.-Chir."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s11940-011-0123-z","article-title":"Subependymal Giant Cell Astrocytoma (SEGA) Treatment Update","volume":"13","author":"Campen","year":"2011","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13023-015-0317-7","article-title":"Rapamycin and its analogues (rapalogs) for Tuberous Sclerosis Complex-associated tumors: A systematic review on non-randomized studies using meta-analysis","volume":"10","author":"Sasongko","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s40120-023-00476-7","article-title":"Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age","volume":"12","author":"Kotulska","year":"2023","journal-title":"Neurol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Tomoto, K., Fujimoto, A., Inenaga, C., Okanishi, T., Imai, S., Ogai, M., Fukunaga, A., Nakamura, H., Sato, K., and Obana, A. (2021). Experience using mTOR inhibitors for subependymal giant cell astrocytoma in tuberous sclerosis complex at a single facility. BMC Neurol., 21.","DOI":"10.1186\/s12883-021-02160-5"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"626","DOI":"10.3892\/etm.2014.2093","article-title":"Efficacy and safety of a mammalian target of rapamycin inhibitor in pediatric patients with tuberous sclerosis complex: A systematic review and meta-analysis","volume":"9","author":"Yang","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.7164\/antibiotics.37.1231","article-title":"Activity of rapamycin (AY-22,989) against transplanted tumors","volume":"37","author":"Eng","year":"1984","journal-title":"J. Antibiot."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1586\/14737140.6.1.131","article-title":"From Rapa Nui to rapamycin: Targeting PI3K\/Akt\/mTOR for cancer therapy","volume":"6","author":"Georgakis","year":"2006","journal-title":"Expert Rev. Anticancer. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12154-008-0003-5","article-title":"Rapamycin and mTOR kinase inhibitors","volume":"1","author":"Ballou","year":"2008","journal-title":"J. Chem. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3660","DOI":"10.1200\/JCO.21.01728","article-title":"nab-Sirolimus for Patients with Malignant Perivascular Epithelioid Cell Tumors","volume":"39","author":"Wagner","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.21873\/anticanres.16360","article-title":"A Phase I\/II Investigation of Safety and Efficacy of Nivolumab and nab-Sirolimus in Patients with a Variety of Tumors with Genetic Mutations in the mTOR Pathway","volume":"43","author":"Gordon","year":"2023","journal-title":"Anticancer. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/00007890-199707150-00008","article-title":"SDZ RAD, a new rapamycin derivative: Pharmacological properties in vitro and in vivo","volume":"64","author":"Schuler","year":"1997","journal-title":"Transplantation"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/S0140-6736(15)00817-X","article-title":"Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): A randomised, placebo-controlled, phase 3 study","volume":"387","author":"Yao","year":"2016","journal-title":"Lancet"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.pharep.2016.01.005","article-title":"Management of side effects of mTOR inhibitors in tuberous sclerosis patients","volume":"68","author":"Sadowski","year":"2016","journal-title":"Pharmacol. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4715","DOI":"10.1021\/ja043277y","article-title":"Characterization of the FKBP.rapamycin.FRB ternary complex","volume":"127","author":"Banaszynski","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"13395","DOI":"10.1074\/jbc.M700498200","article-title":"The Rapamycin-binding Domain of the Protein Kinase Mammalian Target of Rapamycin Is a Destabilizing Domain","volume":"282","author":"Edwards","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s12935-022-02706-8","article-title":"Recent advances and limitations of mTOR inhibitors in the treatment of cancer","volume":"22","author":"Ali","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12943-017-0670-3","article-title":"Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: Current preclinical and clinical development","volume":"16","author":"Zhao","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Hillmann, P., and Fabbro, D. (2019). PI3K\/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225792"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2165\/11207730-000000000-00000","article-title":"Everolimus: In patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex","volume":"14","author":"Curran","year":"2012","journal-title":"Paediatr. Drugs"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/ana.24523","article-title":"Everolimus for subependymal giant cell astrocytoma: 5-year final analysis","volume":"78","author":"Franz","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0140-6736(12)61134-9","article-title":"Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): A multicentre, randomised, placebo-controlled phase 3 trial","volume":"381","author":"Franz","year":"2013","journal-title":"Lancet"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1177\/0883073814544703","article-title":"Everolimus Treatment for an Early Infantile Subependymal Giant Cell Astrocytoma with Tuberous Sclerosis Complex","volume":"30","author":"Fukumura","year":"2015","journal-title":"J. Child Neurol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S1470-2045(14)70489-9","article-title":"Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study","volume":"15","author":"Franz","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1212\/WNL.0b013e3182815428","article-title":"Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma","volume":"80","author":"Krueger","year":"2013","journal-title":"Neurology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pediatrneurol.2014.10.024","article-title":"Long-Term Everolimus Treatment in Individuals with Tuberous Sclerosis Complex: A Review of the Current Literature","volume":"53","author":"Tran","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/S0140-6736(16)31419-2","article-title":"Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): A phase 3, randomised, double-blind, placebo-controlled study","volume":"388","author":"French","year":"2016","journal-title":"Lancet"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/pbc.25368","article-title":"Factors affecting response to everolimus therapy for subependymal giant cell astrocytomas associated with tuberous sclerosis","volume":"62","author":"Trelinska","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.diabres.2015.09.014","article-title":"mTOR inhibitors and diabetes","volume":"110","author":"Cariou","year":"2015","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1158\/0008-5472.CAN-23-0186","article-title":"ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma","volume":"83","author":"Jackson","year":"2023","journal-title":"Cancer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.18632\/oncotarget.13781","article-title":"The therapeutic potential of targeting the PI3K pathway in pediatric brain tumors","volume":"8","author":"Rogers","year":"2017","journal-title":"Oncotarget"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Szklener, K., Mazurek, M., Wieteska, M., Wac\u0142awska, M., Bilski, M., and Ma\u0144dziuk, S. (2022). New Directions in the Therapy of Glioblastoma. Cancers, 14.","DOI":"10.3390\/cancers14215377"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/brain\/awz370","article-title":"The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas","volume":"143","author":"Bongaarts","year":"2020","journal-title":"Brain"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Tang, X., Angst, G., Haas, M., Yang, F., and Wang, C. (2021). The Characterization of a Subependymal Giant Astrocytoma-Like Cell Line from Murine Astrocyte with mTORC1 Hyperactivation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084116"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"239","DOI":"10.5114\/fn.2019.88452","article-title":"Novel small molecule protein kinase CK2 inhibitors exert potent antitumor effects on T98G and SEGA cells in vitro","volume":"57","author":"Pucko","year":"2019","journal-title":"Folia Neuropathol."},{"key":"ref_128","first-page":"95","article-title":"Laser interstitial thermal therapy compared with open resection for treating subependymal giant cell astrocytoma","volume":"33","author":"Aum","year":"2024","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"E9","DOI":"10.3171\/2016.7.FOCUS16231","article-title":"Laser interstitial thermal therapy for subependymal giant cell astrocytoma: Technical case report","volume":"41","author":"Dadey","year":"2016","journal-title":"Neurosurg. Focus"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"100715","DOI":"10.1016\/j.eclinm.2020.100715","article-title":"The metformin in tuberous sclerosis (MiTS) study: A randomised double-blind placebo-controlled trial","volume":"32","author":"Amin","year":"2021","journal-title":"eClinicalMedicine"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/jnen\/nlaa040","article-title":"Dysregulation of the MMP\/TIMP Proteolytic System in Subependymal Giant Cell Astrocytomas in Patients with Tuberous Sclerosis Complex: Modulation of MMP by MicroRNA-320d In Vitro","volume":"79","author":"Bongaarts","year":"2020","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"808","DOI":"10.3171\/2010.9.JNS10816","article-title":"Gamma Knife surgery for subependymal giant cell astrocytomas. Clinical article","volume":"114","author":"Park","year":"2011","journal-title":"J. Neurosurg."},{"key":"ref_133","first-page":"7","article-title":"Temozolomide as Treatment in Lowgrade Glioma: A Systematic Review","volume":"1","author":"Suratos","year":"2016","journal-title":"J. Neuro-Oncol. Neurosci."},{"key":"ref_134","first-page":"39","article-title":"Subependymal giant cell astrocytomas with atypical histological features mimicking malignant gliomas","volume":"49","author":"Grajkowska","year":"2011","journal-title":"Folia Neuropathol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"33623","DOI":"10.18632\/oncotarget.25890","article-title":"Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: A systematic review","volume":"9","author":"Hafazalla","year":"2018","journal-title":"Oncotarget"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e170329","DOI":"10.1172\/JCI170329","article-title":"PI3K\/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma","volume":"134","author":"Duchatel","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Omeljaniuk, W.J., Kr\u0119towski, R., Ratajczak-Wrona, W., Jab\u0142o\u0144ska, E., and Cechowska-Pasko, M. (2021). Novel Dual PI3K\/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111511"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"154145","DOI":"10.1016\/j.prp.2022.154145","article-title":"Voxtalisib and low intensity pulsed ultrasound combinatorial effect on glioblastoma multiforme cancer stem cells via PI3K\/AKT\/mTOR","volume":"239","author":"Tutak","year":"2022","journal-title":"Pathol. Res. Pract."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1093\/neuonc\/nov083","article-title":"Phase I dose-escalation study of the PI3K\/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma","volume":"17","author":"Wen","year":"2015","journal-title":"Neuro Oncol."},{"key":"ref_140","first-page":"1474","article-title":"Metformin for the management of tuberous sclerosis: What does the evidence tell us?","volume":"20","author":"Srinivasan","year":"2021","journal-title":"EXCLI J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S1734-1140(10)70357-1","article-title":"Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide","volume":"62","author":"Suchy","year":"2010","journal-title":"Pharmacol. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ijc.32337","article-title":"Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis","volume":"146","author":"Seliger","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_143","first-page":"e45606","article-title":"Seizing the Connection: Exploring the Interplay between Epilepsy and Glycemic Control in Diabetes Management","volume":"15","author":"Nadeem","year":"2023","journal-title":"Cureus"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.tips.2012.03.001","article-title":"Drug interactions with oral antidiabetic agents: Pharmacokinetic mechanisms and clinical implications","volume":"33","author":"Tornio","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_145","first-page":"2691","article-title":"Potent Antitumour Effects of Novel Pentabromobenzylisothioureas Studied on Human Glial-derived Tumour Cell Lines","volume":"38","author":"Pucko","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1007\/s00381-020-04889-9","article-title":"Current trends in the management of subependymal giant cell astrocytomas in tuberous sclerosis","volume":"36","author":"Frassanito","year":"2020","journal-title":"Child\u2019s Nerv. Syst."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s11060-023-04546-6","article-title":"Laser interstitial thermal therapy for deep-seated perivascular brain tumors is not associated with distal ischemia","volume":"166","author":"Reese","year":"2024","journal-title":"J. Neurooncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1159\/000531210","article-title":"A Comparison of Clinical Outcomes for Subependymal Giant Cell Astrocytomas Treated with Laser Interstitial Thermal Therapy, Open Surgical Resection, and mTOR Inhibitors","volume":"58","author":"Boop","year":"2023","journal-title":"Pediatr. Neurosurg."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3390\/cancers6020625","article-title":"MicroRNAs in the Regulation of MMPs and Metastasis","volume":"6","author":"Abba","year":"2014","journal-title":"Cancers"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ncrna.2022.02.005","article-title":"The role of microRNA in the pathogenesis of glial brain tumors","volume":"7","author":"Beylerli","year":"2022","journal-title":"Non-Coding RNA Res."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Dibdiakova, K., Majercikova, Z., Galanda, T., Richterova, R., Kolarovszki, B., Racay, P., and Hatok, J. (2024). Relationship between the Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Patients with Brain Tumors. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052858"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Zhou, W., Yu, X., Sun, S., Zhang, X., Yang, W., Zhang, J., Zhang, X., and Jiang, Z. (2019). Increased expression of MMP-2 and MMP-9 indicates poor prognosis in glioma recurrence. Biomed. Pharmacother., 118.","DOI":"10.1016\/j.biopha.2019.109369"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"235","DOI":"10.5114\/fn.2023.126886","article-title":"Nanotechnology-based cancer chemoprevention in glioblastoma","volume":"61","author":"Adylova","year":"2023","journal-title":"Folia Neuropathol."},{"key":"ref_154","first-page":"396","article-title":"Engineered smart materials for RNA based molecular therapy to treat Glioblastoma","volume":"33","author":"Singh","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1166\/jnn.2021.18683","article-title":"Study on the Treatment of Tuberous Sclerosis with Rapamycin Nanomicelles Based on Abdominal Ultrasound","volume":"21","author":"Xiao","year":"2021","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5767","DOI":"10.2147\/IJN.S254574","article-title":"Nanotechnology-Based Targeting of mTOR Signaling in Cancer","volume":"15","author":"Yoon","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Jiang, T., Du, J., Wang, J., and Li, C. (2017). Presurgical Administration of mTOR Inhibitors in Patients with Large Subependymal Giant Cell Astrocytoma Associated with Tuberous Sclerosis Complex. World Neurosurg., 107.","DOI":"10.1016\/j.wneu.2017.08.122"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1200\/JCO.23.02266","article-title":"Phase II Trial of nab-Sirolimus in Patients with Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT): Long-Term Efficacy and Safety Update","volume":"42","author":"Wagner","year":"2024","journal-title":"J. Clin. 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