{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:34:45Z","timestamp":1792172085344,"version":"4.4.0"},"reference-count":242,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006595","name":"UEFISCDI, Romania","doi-asserted-by":"publisher","award":["PN-III-P4-ID-PCE-2020-1649"],"award-info":[{"award-number":["PN-III-P4-ID-PCE-2020-1649"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite all of the progress in understanding its molecular biology and pathogenesis, glioblastoma (GBM) is one of the most aggressive types of cancers, and without an efficient treatment modality at the moment, it remains largely incurable. Nowadays, one of the most frequently studied molecules with important implications in the pathogenesis of the classical subtype of GBM is the epidermal growth factor receptor (EGFR). Although many clinical trials aiming to study EGFR targeted therapies have been performed, none of them have reported promising clinical results when used in glioma patients. The resistance of GBM to these therapies was proven to be both acquired and innate, and it seems to be influenced by a cumulus of factors such as ineffective blood\u2013brain barrier penetration, mutations, heterogeneity and compensatory signaling pathways. Recently, it was shown that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. It seems imperative to understand how the EGFR signaling pathways function and how they interconnect with other pathways. Furthermore, it is important to identify the mechanisms of drug resistance and to develop better tailored therapeutic agents.<\/jats:p>","DOI":"10.3390\/ijms241311110","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:34:30Z","timestamp":1688603670000},"page":"11110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["An Overview of EGFR Mechanisms and Their Implications in Targeted Therapies for Glioblastoma"],"prefix":"10.3390","volume":"24","author":[{"given":"Silvia Mara Baez","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Neurosurgical Department, Clinical Emergency Hospital \u201cBagdasar-Arseni\u201d, Soseaua Berceni 12, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Kamel","sequence":"additional","affiliation":[{"name":"Neurosurgical Department, Clinical Emergency Hospital \u201cBagdasar-Arseni\u201d, Soseaua Berceni 12, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gheorghe Vasile","family":"Ciubotaru","sequence":"additional","affiliation":[{"name":"Neurosurgical Department, Clinical Emergency Hospital \u201cBagdasar-Arseni\u201d, Soseaua Berceni 12, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6346-8941","authenticated-orcid":false,"given":"Gelu","family":"Onose","sequence":"additional","affiliation":[{"name":"Neuromuscular Rehabilitation Department, Clinical Emergency Hospital \u201cBagdasar-Arseni\u201d, Soseaua Berceni 12, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani-Simona","family":"Sevastre","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Str. Petru Rares nr. 2\u20134, 710204 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Sfredel","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Str. Petru Rares nr. 2\u20134, 710204 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"Danoiu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Str. Petru Rares nr. 2\u20134, 710204 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3039-857X","authenticated-orcid":false,"given":"Anica","family":"Dricu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Str. Petru Rares nr. 2\u20134, 710204 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6788-5833","authenticated-orcid":false,"given":"Ligia Gabriela","family":"Tataranu","sequence":"additional","affiliation":[{"name":"Neurosurgical Department, Clinical Emergency Hospital \u201cBagdasar-Arseni\u201d, Soseaua Berceni 12, 041915 Bucharest, Romania"},{"name":"Department of Neurosurgery, Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11910-015-0611-8","article-title":"Nitrosoureas in the management of malignant gliomas","volume":"16","author":"Brandes","year":"2016","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1101\/gad.261982.115","article-title":"Cancer stem cells in glioblastoma","volume":"29","author":"Lathia","year":"2015","journal-title":"Genes Dev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rodriguez, S.M.B., Staicu, G.-A., Sevastre, A.-S., Baloi, C., Ciubotaru, V., Dricu, A., and Tataranu, L.G. (2022). Glioblastoma Stem Cells\u2014Useful Tools in the Battle against Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094602"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1056\/NEJMra043666","article-title":"Neural stem cells and the origin of gliomas","volume":"353","author":"Sanai","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1215\/15228517-2007-023","article-title":"Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype","volume":"9","author":"Lim","year":"2007","journal-title":"Neuro-Oncology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3390\/cancers5031049","article-title":"Glioblastoma-initiating cells: Relationship with neural stem cells and the micro-environment","volume":"5","author":"Goffart","year":"2013","journal-title":"Cancers"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Deleanu, R., Ceafalan, L.C., and Dricu, A. (2021). Transcriptomic Crosstalk between Gliomas and Telencephalic Neural Stem and Progenitor Cells for Defining Heterogeneity and Targeted Signaling Pathways. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413211"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1002\/cncr.28968","article-title":"Molecular characterizations of glioblastoma, targeted therapy, and clinical results to date","volume":"121","author":"Bastien","year":"2015","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/00005072-200606000-00001","article-title":"\u2018Pseudopalisading\u2019necrosis in glioblastoma: A familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis","volume":"65","author":"Rong","year":"2006","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11800","DOI":"10.1038\/s41598-018-30296-x","article-title":"Comparative effect of immunotherapy and standard therapy in patients with high grade glioma: A meta-analysis of published clinical trials","volume":"8","author":"Artene","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Alexandru, O., Sevastre, A.-S., Castro, J., Artene, S.-A., Tache, D.E., Purcaru, O.S., Sfredel, V., Tataranu, L.G., and Dricu, A. (2019). Platelet-derived growth factor receptor and ionizing radiation in high grade glioma cell lines. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194663"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization classification of tumors of the central nervous system: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.mpdhp.2011.08.005","article-title":"The pathological diagnosis of diffuse gliomas: Towards a smart synthesis of microscopic and molecular information in a multidisciplinary context","volume":"17","author":"Wesseling","year":"2011","journal-title":"Diagn. Histopathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3109\/07357907.2011.630050","article-title":"Deregulated signaling pathways in glioblastoma multiforme: Molecular mechanisms and therapeutic targets","volume":"30","author":"Mao","year":"2012","journal-title":"Cancer Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"665","DOI":"10.7150\/thno.41692","article-title":"Glioma stem cells and their roles within the hypoxic tumor microenvironment","volume":"11","author":"Boyd","year":"2021","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1159\/000101259","article-title":"Pathologie Anatomy and CT Correlations in the Glioblastoma Multif orme","volume":"46","author":"Burger","year":"1983","journal-title":"Stereotact. Funct. Neurosurg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"rbab062","DOI":"10.1093\/rb\/rbab062","article-title":"Advances in magnetic resonance imaging contrast agents for glioblastoma-targeting theranostics","volume":"8","author":"Wu","year":"2021","journal-title":"Regen. Biomater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1093\/neuonc\/noab013","article-title":"Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients-a report of the PET\/RANO group","volume":"23","author":"Galldiks","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/cac2.12361","article-title":"An update on the molecular biology of glioblastoma, with clinical implications and progress in its treatment","volume":"42","author":"Verdugo","year":"2022","journal-title":"Cancer Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the central nervous system: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1093\/neuonc\/nov013","article-title":"Changes in the EGFR amplification and EGFRvIII expression between paired primary and recurrent glioblastomas","volume":"17","author":"Gao","year":"2015","journal-title":"Neuro-Oncology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.cell.2013.09.034","article-title":"The somatic genomic landscape of glioblastoma","volume":"155","author":"Brennan","year":"2013","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.cell.2015.12.028","article-title":"Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma","volume":"164","author":"Ceccarelli","year":"2016","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ccr.2009.12.020","article-title":"Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1","volume":"17","author":"Verhaak","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.ccr.2010.03.017","article-title":"Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma","volume":"17","author":"Noushmehr","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"Patel","year":"2014","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/s00018-007-6342-5","article-title":"Molecular targets of glioma invasion","volume":"64","author":"Nakada","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Dricu, A. (2022). Oncogenic Signalling of Growth Factor Receptors in Cancer: Mechanisms and Therapeutic Opportunities. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137376"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1126\/science.1075762","article-title":"The protein kinase complement of the human genome","volume":"298","author":"Manning","year":"2002","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0079-6107(98)00047-9","article-title":"Structural analysis of receptor tyrosine kinases","volume":"71","author":"Hubbard","year":"1999","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5548","DOI":"10.1038\/sj.onc.1203957","article-title":"The protein tyrosine kinase family of the human genome","volume":"19","author":"Robinson","year":"2000","journal-title":"Oncogene"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0092-8674(00)00114-8","article-title":"Cell signaling by receptor tyrosine kinases","volume":"103","author":"Schlessinger","year":"2000","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1093\/neuonc\/nox191","article-title":"EGFR heterogeneity and implications for therapeutic intervention in glioblastoma","volume":"20","author":"Eskilsson","year":"2018","journal-title":"Neuro-Oncology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ceb.2009.01.028","article-title":"Tyrosine phosphorylation: Thirty years and counting","volume":"21","author":"Hunter","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.neuron.2006.09.034","article-title":"Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors","volume":"53","author":"Wehrman","year":"2007","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.cell.2006.05.013","article-title":"An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor","volume":"125","author":"Zhang","year":"2006","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.cell.2007.05.055","article-title":"Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor","volume":"130","author":"Yuzawa","year":"2007","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0092-8674(91)90512-W","article-title":"Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor","volume":"64","author":"Yayon","year":"1991","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S1097-2765(00)00073-3","article-title":"Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization","volume":"6","author":"Schlessinger","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nature08827","article-title":"Spatial control of EGF receptor activation by reversible dimerization on living cells","volume":"464","author":"Chung","year":"2010","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1042\/bj2900419","article-title":"Purified hybrid insulin\/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity","volume":"290","author":"Soos","year":"1993","journal-title":"Biochem. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"39684","DOI":"10.1074\/jbc.M202766200","article-title":"Insulin\/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved","volume":"277","author":"Pandini","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/S0969-2126(00)00516-5","article-title":"Structure of the Tie2 RTK domain: Self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail","volume":"8","author":"Shewchuk","year":"2000","journal-title":"Structure"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0092-8674(01)00496-2","article-title":"Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region","volume":"106","author":"Baskin","year":"2001","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.1111\/j.1742-4658.2010.07865.x","article-title":"Docking proteins","volume":"277","author":"Brummer","year":"2010","journal-title":"FEBS J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"55","DOI":"10.5114\/wo.2020.94726","article-title":"Receptor tyrosine kinase targeting in glioblastoma: Performance, limitations and future approaches","volume":"24","author":"Alexandru","year":"2020","journal-title":"Contemp. Oncol.\/Wsp\u00f3\u0142czesna Onkol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1038\/s41388-017-0045-7","article-title":"Epidermal growth factor receptor and EGFRvIII in glioblastoma: Signaling pathways and targeted therapies","volume":"37","author":"An","year":"2018","journal-title":"Oncogene"},{"key":"ref_49","first-page":"31","article-title":"Epidermal growth factor receptor: Mechanisms of activation and signalling","volume":"284","author":"Jorissen","year":"2003","journal-title":"EGF Recept. Fam."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6652","DOI":"10.1158\/0008-5472.CAN-04-1168","article-title":"A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib) relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells","volume":"64","author":"Wood","year":"2004","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev.biophys.37.032807.125829","article-title":"Structure-based view of epidermal growth factor receptor regulation","volume":"37","author":"Ferguson","year":"2008","journal-title":"Annu. Rev. Biophys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.gene.2005.10.018","article-title":"Epidermal growth factor receptor (EGFR) signaling in cancer","volume":"366","author":"Normanno","year":"2006","journal-title":"Gene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"R292","DOI":"10.1016\/S0960-9822(01)00167-1","article-title":"Epidermal growth factor receptor signaling","volume":"11","author":"Bogdan","year":"2001","journal-title":"Curr. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1146\/annurev.biochem.69.1.373","article-title":"Protein tyrosine kinase structure and function","volume":"69","author":"Hubbard","year":"2000","journal-title":"Annu. Rev. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1093\/jnci\/djm187","article-title":"Autocrine factors that sustain glioma invasion and paracrine biology in the brain microenvironment","volume":"99","author":"Hoelzinger","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/35052073","article-title":"Untangling the ErbB signalling network","volume":"2","author":"Yarden","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"800","DOI":"10.3389\/fonc.2019.00800","article-title":"Rethink of EGFR in cancer with its kinase independent function on board","volume":"9","author":"Thomas","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/1878-0261.12155","article-title":"Emerging functions of the EGFR in cancer","volume":"12","author":"Sigismund","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.2147\/OTT.S245169","article-title":"Highly efficient targeting of EGFR-expressing tumor cells with UNiCAR T cells via target modules based on cetuximab\u00ae","volume":"13","author":"Jureczek","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1172\/JCI78239","article-title":"Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment","volume":"125","author":"Tanaka","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1038\/s41388-020-1199-2","article-title":"EGFR activates GDH1 transcription to promote glutamine metabolism through MEK\/ERK\/ELK1 pathway in glioblastoma","volume":"39","author":"Yang","year":"2020","journal-title":"Oncogene"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev.bi.48.070179.001205","article-title":"Epidermal growth factor","volume":"48","author":"Carpenter","year":"1979","journal-title":"Annu. Rev. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"viii1","DOI":"10.1093\/neuonc\/nou294","article-title":"Molecular pathologic diagnosis of epidermal growth factor receptor","volume":"16","author":"Maire","year":"2014","journal-title":"Neuro-Oncology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fmolb.2018.00086","article-title":"The role of PI3K in Met driven cancer: A recap","volume":"5","author":"Hervieu","year":"2018","journal-title":"Front. Mol. Biosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7734","DOI":"10.1128\/MCB.25.17.7734-7742.2005","article-title":"Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface","volume":"25","author":"Dawson","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.cell.2010.06.011","article-title":"Cell signaling by receptor tyrosine kinases","volume":"141","author":"Lemmon","year":"2010","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"eaax2364","DOI":"10.1126\/scisignal.aax2364","article-title":"Blocking EGFR palmitoylation suppresses PI3K signaling and mutant KRAS lung tumorigenesis","volume":"13","author":"Kharbanda","year":"2020","journal-title":"Sci. Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1146\/annurev-med-062913-051343","article-title":"The PI3K\/AKT pathway as a target for cancer treatment","volume":"67","author":"Mayer","year":"2016","journal-title":"Annu. Rev. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mattoon, D.R., Lamothe, B., Lax, I., and Schlessinger, J. (2004). The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K\/Akt cell survival pathway. BMC Biol., 2.","DOI":"10.1186\/1741-7007-2-24"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Mulcahy, E.Q.X., Col\u03ccn, R.R., and Abounader, R. (2020). HGF\/MET signaling in malignant brain tumors. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207546"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"19925","DOI":"10.1074\/jbc.M600482200","article-title":"Scaffolding protein Grb2-associated binder 1 sustains epidermal growth factor-induced mitogenic and survival signaling by multiple positive feedback loops","volume":"281","author":"Kiyatkin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Oprita, A., Baloi, S.-C., Staicu, G.-A., Alexandru, O., Tache, D.E., Danoiu, S., Micu, E.S., and Sevastre, A.-S. (2021). Updated insights on EGFR signaling pathways in glioma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020587"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0092-8674(03)01077-8","article-title":"Specificity in signal transduction: From phosphotyrosine-SH2 domain interactions to complex cellular systems","volume":"116","author":"Pawson","year":"2004","journal-title":"Cell"},{"key":"ref_74","first-page":"3397","article-title":"Targeting oncogenic Ras signaling in hematologic malignancies","volume":"120","author":"Ward","year":"2012","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1172\/JCI31871","article-title":"Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas","volume":"117","author":"Gao","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"ra33","DOI":"10.1126\/scisignal.aac8460","article-title":"JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors","volume":"9","author":"Gao","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fonc.2015.00005","article-title":"Current therapeutic advances targeting EGFR and EGFRvIII in glioblastoma","volume":"5","author":"Padfield","year":"2015","journal-title":"Front. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0962-8924(01)01990-0","article-title":"Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases","volume":"11","year":"2001","journal-title":"Trends Cell Biol."},{"key":"ref_79","first-page":"3767","article-title":"Epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 marker, a novel angiogenesis marker","volume":"8","author":"Serban","year":"2015","journal-title":"OncoTargets Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1093\/hmg\/ddv254","article-title":"Receptor tyrosine kinase mutations in developmental syndromes and cancer: Two sides of the same coin","volume":"24","author":"McDonell","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1126\/science.1235122","article-title":"Cancer genome landscapes","volume":"339","author":"Vogelstein","year":"2013","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1038\/nsmb.2168","article-title":"Mechanistic insights into the activation of oncogenic forms of EGF receptor","volume":"18","author":"Wang","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_83","first-page":"E3595","article-title":"Mechanism for activation of mutated epidermal growth factor receptors in lung cancer","volume":"110","author":"Yun","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ccr.2006.12.017","article-title":"Structures of lung cancer-derived EGFR mutants and inhibitor complexes: Mechanism of activation and insights into differential inhibitor sensitivity","volume":"11","author":"Yun","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S1470-2045(11)70393-X","article-title":"Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial","volume":"13","author":"Rosell","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S1470-2045(11)70184-X","article-title":"Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study","volume":"12","author":"Zhou","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1470-2045(09)70364-X","article-title":"Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial","volume":"11","author":"Mitsudomi","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1056\/NEJMoa0909530","article-title":"Gefitinib or chemotherapy for non\u2013small-cell lung cancer with mutated EGFR","volume":"362","author":"Maemondo","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1200\/JCO.2012.44.2806","article-title":"Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations","volume":"31","author":"Sequist","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1056\/NEJMoa1411817","article-title":"AZD9291 in EGFR inhibitor\u2013resistant non\u2013small-cell lung cancer","volume":"372","author":"Yang","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJMoa1713137","article-title":"Osimertinib in untreated EGFR-mutated advanced non\u2013small-cell lung cancer","volume":"378","author":"Soria","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Lee, J.C., Vivanco, I., Beroukhim, R., Huang, J.H.Y., Feng, W.L., DeBiasi, R.M., Yoshimoto, K., King, J.C., Nghiemphu, P., and Yuza, Y. (2006). Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030485"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1111\/j.1365-2990.2005.00653.x","article-title":"Molecular analysis of the EGFR gene in astrocytic gliomas: mRNA expression, quantitative-PCR analysis of non-homogeneous gene amplification and DNA sequence alterations","volume":"31","author":"Arjona","year":"2005","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_94","first-page":"15249","article-title":"Temozolomide and targeted therapy against epidermal growth factor receptor in glioma","volume":"9","author":"Danciulescu","year":"2016","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1200\/JCO.2008.17.5984","article-title":"Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034","volume":"27","author":"Brandes","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/sj.bjc.6603669","article-title":"Gefitinib in patients with progressive high-grade gliomas: A multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)","volume":"96","author":"Franceschi","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1158\/2159-8290.CD-11-0284","article-title":"Differential sensitivity of glioma-versus lung cancer\u2013specific EGFR mutations to EGFR kinase inhibitors","volume":"2","author":"Vivanco","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/modpathol.2010.62","article-title":"New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile","volume":"23","author":"Benito","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.2353\/ajpath.2007.070011","article-title":"Genetic pathways to primary and secondary glioblastoma","volume":"170","author":"Ohgaki","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S1535-6108(02)00076-4","article-title":"EGF receptor activation by heterologous mechanisms","volume":"1","author":"Carraway","year":"2002","journal-title":"Cancer Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"6009","DOI":"10.1128\/MCB.16.11.6009","article-title":"Transcriptional activation of the human epidermal growth factor receptor promoter by human p53","volume":"16","author":"Subler","year":"1996","journal-title":"Mol. Cell. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1158\/1541-7786.MCR-07-0236","article-title":"Transcription-dependent epidermal growth factor receptor activation by hepatocyte growth factor","volume":"6","author":"Reznik","year":"2008","journal-title":"Mol. Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/ijc.21454","article-title":"EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus","volume":"118","author":"Hanawa","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.cell.2011.02.003","article-title":"Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase","volume":"144","author":"Sun","year":"2011","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.tig.2006.06.007","article-title":"Gene amplification in cancer","volume":"22","author":"Albertson","year":"2006","journal-title":"Trend. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ng1215","article-title":"Chromosome aberrations in solid tumors","volume":"34","author":"Albertson","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1038\/ncomms5846","article-title":"The landscape of kinase fusions in cancer","volume":"5","author":"Stransky","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nature13385","article-title":"Comprehensive molecular profiling of lung adenocarcinoma","volume":"511","author":"Network","year":"2014","journal-title":"Nature"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1056\/NEJMoa042715","article-title":"DNA topoisomerase II in therapy-related acute promyelocytic leukemia","volume":"352","author":"Mistry","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_110","first-page":"2940","article-title":"In vitro irradiation is able to cause RET oncogene rearrangement","volume":"53","author":"Ito","year":"1993","journal-title":"Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1038\/sj.onc.1201313","article-title":"Continued expression of a tissue specific activated oncogene in the early steps of radiation-induced human thyroid carcinogenesis","volume":"15","author":"Mizuno","year":"1997","journal-title":"Oncogene"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Tsai, A.G., and Lieber, M.R. (2010). Mechanisms of chromosomal rearrangement in the human genome. BMC Genom., 11.","DOI":"10.1186\/1471-2164-11-S1-S1"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1158\/2159-8290.CD-16-0075","article-title":"EGFR Fusions as Novel Therapeutic Targets in Lung CancerTherapeutically Targetable EGFR Fusions in Lung Cancer","volume":"6","author":"Konduri","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1158\/2159-8290.CD-14-0377","article-title":"Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions","volume":"4","author":"Lovly","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.cellsig.2005.03.026","article-title":"Autocrine, paracrine and juxtacrine signaling by EGFR ligands","volume":"17","author":"Singh","year":"2005","journal-title":"Cell. Signal."},{"key":"ref_116","first-page":"152","article-title":"Autocrine growth factors and solid tumor malignancy","volume":"155","author":"Walsh","year":"1991","journal-title":"West. J. Med."},{"key":"ref_117","first-page":"2958","article-title":"A novel approach in the treatment of cancer: Targeting the epidermal growth factor receptor","volume":"7","author":"Ciardiello","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Singh, B., Carpenter, G., and Coffey, R.J. (2016). EGF receptor ligands: Recent advances. F1000Research, 5.","DOI":"10.12688\/f1000research.9025.1"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1158\/0008-5472.CAN-05-2753","article-title":"Differential gene expression analysis reveals generation of an autocrine loop by a mutant epidermal growth factor receptor in glioma cells","volume":"66","author":"Ramnarain","year":"2006","journal-title":"Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12943-018-0782-4","article-title":"Mechanisms of receptor tyrosine kinase activation in cancer","volume":"17","author":"Du","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/pcmr.12508","article-title":"Double trouble: Kinase domain duplication as a new path to drug resistance","volume":"29","author":"Chen","year":"2016","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1158\/2159-8290.CD-15-0654","article-title":"EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to AfatinibEGFR-KDD as a Therapeutic Target in Lung and Other Cancers","volume":"5","author":"Gallant","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1365-2990.2008.00977.x","article-title":"Epidermal growth factor receptor extracellular domain mutations in primary glioblastoma","volume":"35","author":"Idbaih","year":"2009","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_124","first-page":"2164","article-title":"Genes for epidermal growth factor receptor, transforming growth factor \u03b1, and epidermal growth factor and their expression in human gliomas in vivo","volume":"51","author":"Ekstrand","year":"1991","journal-title":"Cancer Res."},{"key":"ref_125","first-page":"285","article-title":"Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas","volume":"46","author":"Gullick","year":"1986","journal-title":"Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1517\/14728214.2015.1058778","article-title":"Emerging treatment for advanced lung cancer with EGFR mutation","volume":"20","author":"Inal","year":"2015","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/labinvest.2013.147","article-title":"Epidermal growth factor receptor mutations in lung adenocarcinoma","volume":"94","author":"Siegelin","year":"2014","journal-title":"Lab. Investig."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"851","DOI":"10.2174\/138945010791320773","article-title":"Predictive biomarkers to tyrosine kinase inhibitors for the epidermal growth factor receptor in non-small-cell lung cancer","volume":"11","author":"Normanno","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2353\/jmoldx.2008.070178","article-title":"EGFR mutations in lung adenocarcinomas: Clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression","volume":"10","author":"Li","year":"2008","journal-title":"J. Mol. Diagn."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.pathol.2017.06.001","article-title":"Gene copy number variation and protein overexpression of EGFR and HER2 in distal extrahepatic cholangiocarcinoma","volume":"49","author":"Jung","year":"2017","journal-title":"Pathology"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Birkman, E.-M., \u00c5lgars, A., Lintunen, M., Ristam\u00e4ki, R., Sundstr\u00f6m, J., and Carp\u00e9n, O. (2016). EGFR gene amplification is relatively common and associates with outcome in intestinal adenocarcinoma of the stomach, gastro-oesophageal junction and distal oesophagus. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2456-1"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1242\/jcs.1985.Supplement_3.16","article-title":"Amplification and overexpression of the EGF receptor gene in primary human glioblastomas","volume":"1985","author":"Libermann","year":"1985","journal-title":"J. Cell Sci."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Alexandru, O., Purcaru, S.O., Tataranu, L.G., Lucan, L., Castro, J., Folcu\u0163i, C., Artene, S.-A., Tu\u0163\u0103, C., and Dricu, A. (2018). The influence of EGFR inactivation on the radiation response in high grade glioma. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010229"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1073\/pnas.89.10.4309","article-title":"Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N-and\/or C-terminal tails","volume":"89","author":"Ekstrand","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","first-page":"1816","article-title":"Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors","volume":"8","author":"Yamazaki","year":"1988","journal-title":"Mol. Cell. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1111\/j.1349-7006.2009.01308.x","article-title":"Genetic alterations and signaling pathways in the evolution of gliomas","volume":"100","author":"Ohgaki","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00401-006-0186-1","article-title":"PIK3CA alterations in primary (de novo) and secondary glioblastomas","volume":"113","author":"Kita","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"6892","DOI":"10.1158\/0008-5472.CAN-04-1337","article-title":"Genetic pathways to glioblastoma: A population-based study","volume":"64","author":"Ohgaki","year":"2004","journal-title":"Cancer Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1158\/1078-0432.CCR-12-2246","article-title":"Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung CancersMechanisms of Acquired Resistance to EGFR-TKI Therapy","volume":"19","author":"Yu","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1016\/j.jtho.2016.06.032","article-title":"Acquired resistance to first-line afatinib and the challenges of prearranged progression biopsies","volume":"11","author":"Campo","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0360-3016(01)01609-1","article-title":"EGFR overexpression and radiation response in glioblastoma multiforme","volume":"51","author":"Simmons","year":"2001","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1097\/00006123-199912000-00034","article-title":"Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens","volume":"45","author":"Feldkamp","year":"1999","journal-title":"Neurosurg.-Baltim."},{"key":"ref_143","first-page":"6962","article-title":"Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme","volume":"63","author":"Shinojima","year":"2003","journal-title":"Cancer Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3884","DOI":"10.18632\/oncotarget.6461","article-title":"Overexpression of wildtype EGFR is tumorigenic and denotes a therapeutic target in non-small cell lung cancer","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1126\/science.3500513","article-title":"Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene","volume":"238","author":"Velu","year":"1987","journal-title":"Science"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Greulich, H., Chen, T.-H., Feng, W., J\u00e4nne, P.A., Alvarez, J.V., Zappaterra, M., Bulmer, S.E., Frank, D.A., Hahn, W.C., and Sellers, W.R. (2005). Oncogenic transformation by inhibitor-sensitive and-resistant EGFR mutants. PLoS Med., 2.","DOI":"10.1371\/journal.pmed.0020313"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ctrv.2017.10.008","article-title":"Epidermal growth factor receptor overexpression and outcomes in early breast cancer: A systematic review and a meta-analysis","volume":"62","author":"Templeton","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2478\/raon-2014-0015","article-title":"EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides","volume":"49","author":"Carlsson","year":"2015","journal-title":"Radiol. Oncol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1750-3639.2004.tb00045.x","article-title":"Predominant expression of mutant EGFR (EGFRvIII) is rare in primary glioblastomas","volume":"14","author":"Biernat","year":"2004","journal-title":"Brain Pathol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.oooo.2018.02.014","article-title":"EGFR is not amplified in ameloblastoma","volume":"125","author":"Costa","year":"2018","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/13543784.2017.1299707","article-title":"Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer","volume":"26","author":"Matsuda","year":"2017","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1093\/neuonc\/nov319","article-title":"Epidermal growth factor receptor targeting and challenges in glioblastoma","volume":"18","author":"Thorne","year":"2016","journal-title":"Neuro-Oncology"},{"key":"ref_153","first-page":"1927","article-title":"Molecularly targeted therapy for the treatment of head and neck cancer: A review of the ErbB family inhibitors","volume":"9","author":"Sacco","year":"2016","journal-title":"OncoTargets Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.jhep.2012.04.034","article-title":"Erlotinib and sorafenib in an orthotopic rat model of hepatocellular carcinoma","volume":"57","author":"Sieghart","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1038\/bjc.2011.396","article-title":"Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells","volume":"105","author":"Ioannou","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ccr.2008.03.015","article-title":"Survival of cancer cells is maintained by EGFR independent of its kinase activity","volume":"13","author":"Weihua","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1158\/0008-5472.CAN-15-2121","article-title":"The EGF Receptor Promotes the Malignant Potential of Glioma by Regulating Amino Acid Transport System xc (\u2212) EGFR Regulates xCT in Glioma","volume":"76","author":"Tsuchihashi","year":"2016","journal-title":"Cancer Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0014-4827(02)00050-2","article-title":"Small interfering RNAs suppress the expression of endogenous and GFP-fused epidermal growth factor receptor (erbB1) and induce apoptosis in erbB1-overexpressing cells","volume":"285","author":"Nagy","year":"2003","journal-title":"Exp. Cell Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s11060-004-8322-z","article-title":"An in vitro study on the suppressive effect of glioma cell growth induced by plasmid-based small interference RNA (siRNA) targeting human epidermal growth factor receptor","volume":"74","author":"Kang","year":"2005","journal-title":"J. Neuro-Oncol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bbrc.2012.12.070","article-title":"Effect of siRNAs targeting the EGFR T790M mutation in a non-small cell lung cancer cell line resistant to EGFR tyrosine kinase inhibitors and combination with various agents","volume":"431","author":"Chen","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1158\/2159-8290.CD-13-0879","article-title":"EGFR Variant Heterogeneity in Glioblastoma Resolved through Single-Nucleus SequencingSingle-Nucleus Sequencing of GBM Mutational Heterogeneity","volume":"4","author":"Francis","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.ccr.2011.11.005","article-title":"Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma","volume":"20","author":"Snuderl","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1056\/NEJMoa051918","article-title":"Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors","volume":"353","author":"Mellinghoff","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1093\/neuonc\/not247","article-title":"Phase I\/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02","volume":"16","author":"Wen","year":"2014","journal-title":"Neuro-Oncology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1200\/JCO.2006.08.0705","article-title":"Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma","volume":"25","author":"Pelloski","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/BF02484510","article-title":"Immunohistochemical analysis of the mutant epidermal growth factor, \u0394EGFR, in glioblastoma","volume":"21","author":"Nishikawa","year":"2004","journal-title":"Brain Tumor Pathol."},{"key":"ref_167","first-page":"1383","article-title":"Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas","volume":"60","author":"Frederick","year":"2000","journal-title":"Cancer Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"7587","DOI":"10.1158\/0008-5472.CAN-11-0821","article-title":"Glioblastoma-Derived Epidermal Growth Factor Receptor Carboxyl-Terminal Deletion Mutants Are Transforming and Are Sensitive to EGFR-Directed TherapiesStudy of GBM-Derived EGFR C-Terminal Deletion Mutants","volume":"71","author":"Cho","year":"2011","journal-title":"Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/ng.2734","article-title":"The integrated landscape of driver genomic alterations in glioblastoma","volume":"45","author":"Frattini","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Shah, N., Lankerovich, M., Lee, H., Yoon, J.-G., Schroeder, B., and Foltz, G. (2013). Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-818"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.compbiomed.2018.10.021","article-title":"Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis","volume":"103","author":"Hu","year":"2018","journal-title":"Comput. Biol. Med."},{"key":"ref_172","unstructured":"Donzelli, S., Cioce, M., Muti, P., Strano, S., Yarden, Y., and Blandino, G. (2016). Seminars in Cell & Developmental Biology, Academic Press."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Khan, A.Q., Ahmed, E.I., Elareer, N.R., Junejo, K., Steinhoff, M., and Uddin, S. (2019). Role of miRNA-regulated cancer stem cells in the pathogenesis of human malignancies. Cells, 8.","DOI":"10.3390\/cells8080840"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.biopha.2017.07.010","article-title":"Melatonin inhibits proliferation and invasion via repression of miRNA-155 in glioma cells","volume":"93","author":"Gu","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_175","first-page":"1939","article-title":"miRNA-320a inhibits glioma cell invasion and migration by directly targeting aquaporin 4","volume":"39","author":"Xiong","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jbior.2014.09.013","article-title":"MicroRNA and cancer\u2013a brief overview","volume":"57","author":"Acunzo","year":"2015","journal-title":"Adv. Biol. Regul."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Rao, S.A.M., Arimappamagan, A., Pandey, P., Santosh, V., Hegde, A.S., Chandramouli, B.A., and Somasundaram, K. (2013). miR-219-5p inhibits receptor tyrosine kinase pathway by targeting EGFR in glioblastoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063164"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/cdd.2013.196","article-title":"Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma","volume":"21","author":"Zhang","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.canlet.2013.08.043","article-title":"Blockage of a miR-21\/EGFR regulatory feedback loop augments anti-EGFR therapy in glioblastomas","volume":"342","author":"Zhang","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1126\/science.1142946","article-title":"Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies","volume":"318","author":"Stommel","year":"2007","journal-title":"Science"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.4161\/cc.6.22.4922","article-title":"Uncovering therapeutic targets for glioblastoma: A systems biology approach","volume":"6","author":"Huang","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ccr.2014.02.025","article-title":"ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics","volume":"25","author":"Arteaga","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Yamaoka, T., Ohba, M., and Ohmori, T. (2017). Molecular-targeted therapies for epidermal growth factor receptor and its resistance mechanisms. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112420"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1056\/NEJMoa1006448","article-title":"Anaplastic lymphoma kinase inhibition in non\u2013small-cell lung cancer","volume":"363","author":"Kwak","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1056\/NEJMoa0810699","article-title":"Gefitinib or carboplatin\u2013paclitaxel in pulmonary adenocarcinoma","volume":"361","author":"Mok","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1038\/onc.2008.109","article-title":"BIBW2992, an irreversible EGFR\/HER2 inhibitor highly effective in preclinical lung cancer models","volume":"27","author":"Li","year":"2008","journal-title":"Oncogene"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"7665","DOI":"10.1073\/pnas.0502860102","article-title":"Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib","volume":"102","author":"Kwak","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_188","unstructured":"Finlay, M.R.V., Anderton, M., Ashton, S., Ballard, P., Bethel, P.A., Box, M.R., Bradbury, R.H., Brown, S.J., Butterworth, S., and Campbell, A. (2014). Discovery of a Potent and Selective EGFR Inhibitor (AZD9291) of Both Sensitizing and T790M Resistance Mutations That Spares the Wild Type Form of the Receptor, ACS Publications."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1158\/2159-8290.CD-14-0326","article-title":"Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor\u2013Resistant EGFR-Mutant Lung Cancer with and without T790M MutationsDual EGFR Inhibition in TKI-Resistant, EGFR-Mutant NSCLC","volume":"4","author":"Janjigian","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/nature08622","article-title":"Novel mutant-selective EGFR kinase inhibitors against EGFR T790M","volume":"462","author":"Zhou","year":"2009","journal-title":"Nature"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"e576","DOI":"10.1016\/j.cllc.2019.05.003","article-title":"Outcome differences between first-and second-generation EGFR inhibitors in advanced EGFR mutated NSCLC in a large population-based cohort","volume":"20","author":"Lau","year":"2019","journal-title":"Clin. Lung Cancer"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1158\/2159-8290.CD-13-0314","article-title":"Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLCDevelopment of Covalent EGFRT790M Inhibitor in NSCLC","volume":"3","author":"Walter","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.canlet.2016.11.008","article-title":"EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance","volume":"385","author":"Wang","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Wee, P., and Wang, Z. (2017). Epidermal growth factor receptor cell proliferation signaling pathways. Cancers, 9.","DOI":"10.3390\/cancers9050052"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"iv61","DOI":"10.1093\/annonc\/mdi910","article-title":"Sequence-dependent antiproliferative effects of cytotoxic drugs and epidermal growth factor receptor inhibitors","volume":"16","author":"Morelli","year":"2005","journal-title":"Ann. Oncol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4161\/cc.27518","article-title":"EGFR signaling and autophagy dependence for growth, survival, and therapy resistance","volume":"13","author":"Jutten","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Henson, E., Chen, Y., and Gibson, S. (2017). EGFR family members\u2019 regulation of autophagy is at a crossroads of cell survival and death in cancer. Cancers, 9.","DOI":"10.3390\/cancers9040027"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1002\/pros.22692","article-title":"EGFR\u2013SGLT1 interaction does not respond to EGFR modulators, but inhibition of SGLT1 sensitizes prostate cancer cells to EGFR tyrosine kinase inhibitors","volume":"73","author":"Ren","year":"2013","journal-title":"Prostate"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1158\/1535-7163.MCT-11-0048","article-title":"Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib\u2014A phase II trial","volume":"10","author":"Hegi","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ijrobp.2010.01.070","article-title":"Phase II evaluation of gefitinib in patients with newly diagnosed Grade 4 astrocytoma: Mayo\/North Central Cancer Treatment Group Study N0074","volume":"80","author":"Uhm","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/neuonc\/nop015","article-title":"A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy","volume":"12","author":"Raizer","year":"2010","journal-title":"Neuro-Oncology"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/jnci\/dji161","article-title":"Epidermal growth factor receptor, protein kinase B\/Akt, and glioma response to erlotinib","volume":"97","author":"Prados","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00280-009-1041-6","article-title":"A phase I\/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: Clinical outcomes, pharmacokinetics and molecular correlation","volume":"65","author":"Thiessen","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_204","first-page":"430","article-title":"Phase I\/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma","volume":"17","author":"Reardon","year":"2015","journal-title":"Neuro-Oncology"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1158\/1535-7163.MCT-20-0640","article-title":"In Vivo Efficacy of Tesevatinib in EGFR-Amplified Patient-Derived Xenograft Glioblastoma Models May Be Limited by Tissue Binding and Compensatory SignalingTesevatinib Brain PK and Efficacy in GBM PDX Models","volume":"20","author":"Kizilbash","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1080\/13543784.2018.1528225","article-title":"Dacomitinib: An investigational drug for the treatment of glioblastoma","volume":"27","author":"Gargini","year":"2018","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1158\/1535-7163.MCT-19-0819","article-title":"Comparison of Panitumumab-IRDye800CW and 5-Aminolevulinic Acid to Provide Optical Contrast in a Model of Glioblastoma MultiformePanitumumab-IRDye800CW versus 5-ALA for Optical Contrast","volume":"19","author":"Napier","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Wang, Q., Ni, J., Jiang, T., Choi, H.G., Zhang, T., Gray, N., and Zhao, J.J. (2020). CM93, a novel covalent small molecule inhibitor targeting lung cancer with mutant EGFR. BioRxiv.","DOI":"10.1101\/2020.03.09.984500"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Ni, J., Yang, Y., Wang, Q., Bergholz, J.S., Jiang, T., Roberts, T.M., Gray, N.S., and Zhao, J.J. (2021). Targeting EGFR in glioblastoma with a novel brain-penetrant small molecule EGFR-TKI. BioRxiv.","DOI":"10.1101\/2021.01.09.426030"},{"key":"ref_210","unstructured":"Erasca (2023, February 20). Erasca Granted FDA Orphan Drug Designation for CNS-Penetrant EGFR Inhibitor ERAS-801 for the Treatment of Malignant Glioma. Available online: https:\/\/investors.erasca.com\/news-releases\/news-release-details\/erasca-granted-fda-orphan-drug-designation-cns-penetrant-egfr."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"vdad066","DOI":"10.1093\/noajnl\/vdad066","article-title":"WSD-0922, a novel brain-penetrant inhibitor of epidermal growth factor receptor, promotes survival in glioblastoma mouse models","volume":"5","author":"Stopka","year":"2023","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1442-200X.2010.03220.x","article-title":"Response to nimotuzumab in a child with a progressive diffuse intrinsic pontine glioma","volume":"53","author":"Mateos","year":"2011","journal-title":"Pediatr. Int."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.2217\/fon.09.119","article-title":"Nimotuzumab in pediatric glioma","volume":"5","author":"Lam","year":"2009","journal-title":"Future Oncol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"912","DOI":"10.4161\/cbt.5.8.3118","article-title":"Long term responses with cetuximab therapy in glioblastoma multiforme","volume":"5","author":"Saenz","year":"2006","journal-title":"Cancer Biol. Ther."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1227\/01.NEU.0000145865.25689.55","article-title":"Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo","volume":"56","author":"Eller","year":"2005","journal-title":"Neurosurgery"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1093\/annonc\/mdp032","article-title":"Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma","volume":"20","author":"Neyns","year":"2009","journal-title":"Ann. Oncol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1073\/pnas.1219817110","article-title":"Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma","volume":"110","author":"Choi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"10009","DOI":"10.1073\/pnas.1821442116","article-title":"Oncogenic mutations at the EGFR ectodomain structurally converge to remove a steric hindrance on a kinase-coupled cryptic epitope","volume":"116","author":"Orellana","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.ijrobp.2010.03.027","article-title":"MAb 806 enhances the efficacy of ionizing radiation in glioma xenografts expressing the de2-7 epidermal growth factor receptor","volume":"78","author":"Johns","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"275ra222","DOI":"10.1126\/scitranslmed.aaa4963","article-title":"Rational development and characterization of humanized anti\u2013EGFR variant III chimeric antigen receptor T cells for glioblastoma","volume":"7","author":"Johnson","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"108734","DOI":"10.1016\/j.biopha.2019.108734","article-title":"Antitumor efficacy of chimeric antigen receptor T cells against EGFRvIII-expressing glioblastoma in C57BL\/6 mice","volume":"113","author":"Chen","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"eaaa0984","DOI":"10.1126\/scitranslmed.aaa0984","article-title":"A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma","volume":"9","author":"Nasrallah","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1097\/CJI.0000000000000260","article-title":"Pilot trial of adoptive transfer of chimeric antigen receptor transduced T cells targeting EGFRvIII in patients with glioblastoma","volume":"42","author":"Goff","year":"2019","journal-title":"J. Immunother."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"S510","DOI":"10.21037\/tcr.2018.03.36","article-title":"Lessons learned from rindopepimut treatment in patients with EGFRvIII-expressing glioblastoma","volume":"7","author":"Binder","year":"2018","journal-title":"Transl. Cancer Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1093\/neuonc\/nou348","article-title":"A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: The ACT III study","volume":"17","author":"Schuster","year":"2015","journal-title":"Neuro-Oncology"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S1470-2045(17)30517-X","article-title":"Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): A randomised, double-blind, international phase 3 trial","volume":"18","author":"Weller","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1158\/1535-7163.MCT-22-0201","article-title":"A novel EGFRvIII T-cell bispecific antibody for the treatment of glioblastoma","volume":"21","author":"Iurlaro","year":"2022","journal-title":"Mol. Cancer Ther."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3171\/2010.2.JNS091211","article-title":"A phase II study of anti\u2013epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme","volume":"113","author":"Li","year":"2010","journal-title":"J. Neurosurg."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jconrel.2016.02.026","article-title":"Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the-art","volume":"227","author":"Karim","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"209205","DOI":"10.1155\/2013\/209205","article-title":"Targeted antiepidermal growth factor receptor (cetuximab) immunoliposomes enhance cellular uptake in vitro and exhibit increased accumulation in an intracranial model of glioblastoma multiforme","volume":"2013","author":"Mortensen","year":"2013","journal-title":"J. Drug Deliv."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ejca.2016.10.017","article-title":"Nuclear transportation of exogenous epidermal growth factor receptor and androgen receptor via extracellular vesicles","volume":"70","author":"Read","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1158\/0008-5472.CAN-15-3432","article-title":"Extracellular Vesicles from High-Grade Glioma Exchange Diverse Pro-oncogenic Signals That Maintain Intratumoral HeterogeneityTumor Heterogeneity Is Enhanced by Extracellular Vesicles","volume":"76","author":"Ricklefs","year":"2016","journal-title":"Cancer Res."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.drup.2019.04.002","article-title":"The TICking clock of EGFR therapy resistance in glioblastoma: Target Independence or target Compensation","volume":"43","author":"Saleem","year":"2019","journal-title":"Drug Resist. Updat."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1126\/science.1241328","article-title":"Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA","volume":"343","author":"Nathanson","year":"2014","journal-title":"Science"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1158\/1535-7163.MCT-16-0105","article-title":"Strategies to overcome bypass mechanisms mediating clinical resistance to EGFR tyrosine kinase inhibition in lung cancer","volume":"16","author":"Husain","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ctrv.2018.02.006","article-title":"Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: Mechanisms and therapeutic strategies","volume":"65","author":"Lim","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrclinonc.2014.104","article-title":"Acquired resistance to TKIs in solid tumours: Learning from lung cancer","volume":"11","author":"Camidge","year":"2014","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1183\/09059180.00004614","article-title":"Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas","volume":"23","author":"Cortot","year":"2014","journal-title":"Eur. Respir. Rev."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41598-019-57153-9","article-title":"Targeting of EGFR by a combination of antibodies mediates unconventional EGFR trafficking and degradation","volume":"10","author":"Jones","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2174\/1568009616666161215162515","article-title":"The role of EGFR-Met interactions in the pathogenesis of glioblastoma and resistance to treatment","volume":"17","author":"Guo","year":"2017","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1517\/14728214.2015.1031653","article-title":"Emerging drugs for head and neck cancer","volume":"20","author":"Wen","year":"2015","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1038\/onc.2012.280","article-title":"EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms","volume":"32","author":"Giacomini","year":"2013","journal-title":"Oncogene"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/11110\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:06:25Z","timestamp":1760126785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/11110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,5]]},"references-count":242,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241311110"],"URL":"https:\/\/doi.org\/10.3390\/ijms241311110","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,5]]}}}