Glioma Stem Cells in Pediatric High-Grade Gliomas: From Current Knowledge to Future Perspectives.

cancer stem cell; diffuse intrinsic pontine glioma; diffuse midline glioma; glioblastoma; glioma initiating cell; glioma stem cell; pediatric high-grade glioma; subventricular zone; Oncology; Cancer Research

Abstract :

[en] In children, high-grade gliomas (HGG) and diffuse midline gliomas (DMG) account for a high proportion of death due to cancer. Glioma stem cells (GSCs) are tumor cells in a specific state defined by a tumor-initiating capacity following serial transplantation, self-renewal, and an ability to recapitulate tumor heterogeneity. Their presence was demonstrated several decades ago in adult glioblastoma (GBM), and more recently in pediatric HGG and DMG. In adults, we and others have previously suggested that GSCs nest into the subventricular zone (SVZ), a neurogenic niche, where, among others, they find shelter from therapy. Both bench and bedside evidence strongly indicate a role for the GSCs and the SVZ in GBM progression, fostering the development of innovative targeting treatments. Such new therapeutic approaches are of particular interest in infants, in whom standard therapies are often limited due to the risk of late effects. The aim of this review is to describe current knowledge about GSCs in pediatric HGG and DMG, i.e., their characterization, the models that apply to their development and maintenance, the specific signaling pathways that may underlie their activity, and their specific interactions with neurogenic niches. Finally, we will discuss the clinical relevance of these observations and the therapeutic advantages of targeting the SVZ and/or the GSCs in infants.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Da Veiga, Marc-Antoine ; Université de Liège - ULiège > GIGA

Rogister, Bernard ; Centre Hospitalier Universitaire de Liège - CHU > > Service de neurologie

LOMBARD, Arnaud ; Centre Hospitalier Universitaire de Liège - CHU > > Service de neurochirurgie

Neirinckx, Virginie ^✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques

PIETTE, Caroline ^✱; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie

^✱ These authors have contributed equally to this work.

Language :

English

Title :

Glioma Stem Cells in Pediatric High-Grade Gliomas: From Current Knowledge to Future Perspectives.

Publication date :

04 May 2022

Journal title :

Cancers

eISSN :

2072-6694

Publisher :

MDPI, Switzerland

Volume :

Issue :

Pages :

2296

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.mdpi.com/2072-6694/14/9/2296/pdf

Funders :

F.R.S.-FNRS - Fund for Scientific Research [BE]

Funding text :

M.-A.D.-V. is a Ph.D. student funded by the TELEVIE-FNRS and the EUROMA funds (Fondation L?on Fr?d?ricq, University of Li?ge); AL received the Clinical Researcher of the FNRS-Belgium; BR research group is supported by the FNRS, the TELEVIE, the University of Li?ge and the Fondation L?on Fr?d?ricq.Funding: M.-A.D.-V. is a Ph.D. student funded by the TELEVIE-FNRS and the EUROMA funds (Fondation Léon Frédéricq, University of Liège); AL received the Clinical Researcher of the FNRS-Belgium; BR research group is supported by the FNRS, the TELEVIE, the University of Liège and the Fondation Léon Frédéricq.

Available on ORBi :

since 27 May 2022

Statistics

Number of views

109 (9 by ULiège)

Number of downloads

41 (3 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Ostrom, Q.T.; Patil, N.; Cioffi, G.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013–2017. Neuro-Oncology 2020, 22, IV1–IV96. https://doi.org/10.1093/NEUONC/NOAA200.
Ostrom, Q.T.; de Blank, P.M.; Kruchko, C.; Petersen, C.M.; Liao, P.; Finlay, J.L.; Stearns, D.S.; Wolff, J.E.; Wolinsky, Y.; Letterio, J.J.; et al. Alex’s Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011. Neuro-Oncology 2015, 16 (Suppl. 10), x1–x35. https://doi.org/10.1093/NEUONC/NOU327.
Louis, D.N.; Perry, A.; Wesseling, P.; Brat, D.J.; Cree, I.A.; Figarella-Branger, D.; Hawkins, C.; Ng, H.K.; Pfister, S.M.; Reifenberger, G.; et al. The 2021 WHO Classification of Tumors of the Central Nervous System: A Summary. Neuro-Oncology 2021, 23, 1231–1251. https://doi.org/10.1093/NEUONC/NOAB106.
Louis, D.N.; Perry, A.; Reifenberger, G.; von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K.; Ohgaki, H.; Wiestler, O.D.; Kleihues, P.; Ellison, D.W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary. Acta Neuropathol. 2016, 131, 803–820. https://doi.org/10.1007/S00401-016-1545-1.
Sturm, D.; Witt, H.; Hovestadt, V.; Khuong-Quang, D.A.; Jones, D.T.W.; Konermann, C.; Pfaff, E.; Tönjes, M.; Sill, M.; Bender, S.; et al. Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma. Cancer Cell 2012, 22, 425–437. https://doi.org/10.1016/J.CCR.2012.08.024.
Bender, S.; Tang, Y.; Lindroth, A.M.; Hovestadt, V.; Jones, D.T.W.; Kool, M.; Zapatka, M.; Northcott, P.A.; Sturm, D.; Wang, W.; et al. Reduced H3K27me3 and DNA Hypomethylation Are Major Drivers of Gene Expression in K27M Mutant Pediatric High-Grade Gliomas. Cancer Cell 2013, 24, 660–672. https://doi.org/10.1016/J.CCR.2013.10.006.
Lewis, P.W.; Müller, M.M.; Koletsky, M.S.; Cordero, F.; Lin, S.; Banaszynski, L.A.; Garcia, B.A.; Muir, T.W.; Becher, O.J.; Allis, C.D. Inhibition of PRC2 Activity by a Gain-of-Function H3 Mutation Found in Pediatric Glioblastoma. Science 2013, 340, 857– 861. https://doi.org/10.1126/SCIENCE.1232245.
Chan, K.M.; Fang, D.; Gan, H.; Hashizume, R.; Yu, C.; Schroeder, M.; Gupta, N.; Mueller, S.; David James, C.; Jenkins, R.; et al. The Histone H3.3K27M Mutation in Pediatric Glioma Reprograms H3K27 Methylation and Gene Expression. Genes Dev. 2013, 27, 985. https://doi.org/10.1101/GAD.217778.113.
Herz, H.M.; Morgan, M.; Gao, X.; Jackson, J.; Rickels, R.; Swanson, S.K.; Florens, L.; Washburn, M.P.; Eissenberg, J.C.; Shilatifard, A. Histone H3 Lysine-to-Methionine Mutants as a Paradigm to Study Chromatin Signaling. Science 2014, 345, 1065–1070. https://doi.org/10.1126/SCIENCE.1255104.
Lee, J.; Solomon, D.A.; Tihan, T. The Role of Histone Modifications and Telomere Alterations in the Pathogenesis of Diffuse Gliomas in Adults and Children. J. Neurooncol. 2017, 132, 1–11. https://doi.org/10.1007/S11060-016-2349-9.
Castel, D.; Kergrohen, T.; Tauziède-Espariat, A.; Mackay, A.; Ghermaoui, S.; Lechapt, E.; Pfister, S.M.; Kramm, C.M.; Boddaert, N.; Blauwblomme, T.; et al. Histone H3 Wild-Type DIPG/DMG Overexpressing EZHIP Extend the Spectrum Diffuse Midline Gliomas with PRC2 Inhibition beyond H3-K27M Mutation. Acta Neuropathol. 2020, 139, 1109–1113. https://doi.org/10.1007/S00401-020-02142-W/FIGURES/2.
Lowe, B.R.; Maxham, L.A.; Hamey, J.J.; Wilkins, M.R.; Partridge, J.F. Histone H3 Mutations: An Updated View of Their Role in Chromatin Deregulation and Cancer. Cancers (Basel) 2019, 11, 660. https://doi.org/10.3390/CANCERS11050660.
Korshunov, A.; Schrimpf, D.; Ryzhova, M.; Sturm, D.; Chavez, L.; Hovestadt, V.; Sharma, T.; Habel, A.; Burford, A.; Jones, C.; et al. H3-/IDH-Wild Type Pediatric Glioblastoma Is Comprised of Molecularly and Prognostically Distinct Subtypes with Associated Oncogenic Drivers. Acta Neuropathol. 2017, 134, 507–516. https://doi.org/10.1007/S00401-017-1710-1.
Clarke, M.; Mackay, A.; Ismer, B.; Pickles, J.C.; Tatevossian, R.G.; Newman, S.; Bale, T.A.; Stoler, I.; Izquierdo, E.; Temelso, S.; et al. Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes. Cancer Discov. 2020, 10, 942–963. https://doi.org/10.1158/2159-8290.CD-19-1030/333425/AM/INFANT-HIGH-GRADE-GLIOMAS-COMPRISE-MULTIPLE.
van Zanten, S.E.M.V.; Jansen, M.H.; Sanchez Aliaga, E.; van Vuurden, D.G.; Vandertop, W.P.; Kaspers, G.J. A Twenty-Year Review of Diagnosing and Treating Children with Diffuse Intrinsic Pontine Glioma in The Netherlands. Expert Rev. Anticancer Ther. 2015, 15, 157–164. https://doi.org/10.1586/14737140.2015.974563.
Hall, M.D.; Odia, Y.; Allen, J.E.; Tarapore, R.; Khatib, Z.; Niazi, T.N.; Daghistani, D.; Schalop, L.; Chi, A.S.; Oster, W.; et al. First Clinical Experience with DRD2/3 Antagonist ONC201 in H3 K27M–Mutant Pediatric Diffuse Intrinsic Pontine Glioma: A Case Report. J. Neurosurg. Pediatrics 2019, 23, 719–725. https://doi.org/10.3171/2019.2.PEDS18480.
Aziz-Bose, R.; Monje, M. Diffuse Intrinsic Pontine Glioma: Molecular Landscape and Emerging Therapeutic Targets. Curr. Opin. Oncol. 2019, 31, 522–530. https://doi.org/10.1097/CCO.0000000000000577.
Cooney, T.; Lane, A.; Bartels, U.; Bouffet, E.; Goldman, S.; Leary, S.E.S.; Foreman, N.K.; Packer, R.J.; Broniscer, A.; Minturn, J.E.; et al. Contemporary Survival Endpoints: An International Diffuse Intrinsic Pontine Glioma Registry Study. Neuro-Oncology 2017, 19, 1279–1280. https://doi.org/10.1093/NEUONC/NOX107.
da Costa, M.D.S.; Camargo, N.C.; Dastoli, P.A.; Nicácio, J.M.; Benevides Silva, F.A.; Sucharski Figueiredo, M.L.; Chen, M.J.; Cappellano, A.M.; da Silva, N.S.; Cavalheiro, S. High-Grade Gliomas in Children and Adolescents: Is There a Role for Reoperation? J. Neurosurg. Pediatr. 2020, 27, 160–169. https://doi.org/10.3171/2020.7.PEDS20389.
Jones, C.; Karajannis, M.A.; Jones, D.T.W.; Kieran, M.W.; Monje, M.; Baker, S.J.; Becher, O.J.; Cho, Y.J.; Gupta, N.; Hawkins, C.; et al. Pediatric High-Grade Glioma: Biologically and Clinically in Need of New Thinking. Neuro-Oncology 2017, 19, 153–161. https://doi.org/10.1093/NEUONC/NOW101.
Zakrzewski, W.; Dobrzyński, M.; Szymonowicz, M.; Rybak, Z. Stem Cells: Past, Present, and Future. Stem Cell Res. Ther. 2019, 10, 68. https://doi.org/10.1186/S13287-019-1165-5/FIGURES/8.
Doulatov, S.; Notta, F.; Laurenti, E.; Dick, J.E. Hematopoiesis: A Human Perspective. Cell Stem Cell 2012, 10, 120–136. https://doi.org/10.1016/J.STEM.2012.01.006.
Clevers, H. The Intestinal Crypt, a Prototype Stem Cell Compartment. Cell 2013, 154, 274. https://doi.org/10.1016/J.CELL.2013.07.004.
Temple, S. The Development of Neural Stem Cells. Nature 2001, 414, 112–117. https://doi.org/10.1038/35102174.
Al-Hajj, M.; Wicha, M.S.; Benito-Hernandez, A.; Morrison, S.J.; Clarke, M.F. Prospective Identification of Tumorigenic Breast Cancer Cells. Proc. Natl. Acad. Sci. USA 2003, 100, 3983–3988. https://doi.org/10.1073/PNAS.0530291100.
Furth, J.; Kahn, M.C. The Transmission of Leukemia of Mice with a Single Cell. Am. J. Cancer 1937, 31, 276–282. https://doi.org/10.1158/AJC.1937.276.
Lapidot, T.; Sirard, C.; Vormoor, J.; Murdoch, B.; Hoang, T.; Caceres-Cortes, J.; Minden, M.; Paterson, B.; Caligiuri, M.A.; Dick, J.E. A Cell Initiating Human Acute Myeloid Leukaemia after Transplantation into SCID Mice. Nature 1994, 367, 645–648. https://doi.org/10.1038/367645a0.
Bonnet, D.; Dick, J.E. Human Acute Myeloid Leukemia Is Organized as a Hierarchy That Originates from a Primitive Hematopoietic Cell. Nat. Med. 1997, 3, 730–737. https://doi.org/10.1038/nm0797-730.
Clevers, H. The Cancer Stem Cell: Premises, Promises and Challenges. Nat. Med. 2011, 17, 313–319. https://doi.org/10.1038/NM.2304.
Singh, S.K.; Hawkins, C.; Clarke, I.D.; Squire, J.A.; Bayani, J.; Hide, T.; Henkelman, R.M.; Cusimano, M.D.; Dirks, P.B. Identification of Human Brain Tumour Initiating Cells. Nature 2004, 432, 396–401. https://doi.org/10.1038/nature03128.
Galli, R.; Binda, E.; Orfanelli, U.; Cipelletti, B.; Gritti, A.; de Vitis, S.; Fiocco, R.; Foroni, C.; Dimeco, F.; Vescovi, A. Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma. Cancer Res. 2004, 64, 7011–7021. https://doi.org/10.1158/0008-5472.CAN-04-1364.
Reynolds, B.A.; Weiss, S. Generation of Neurons and Astrocytes from Isolated Cells of the Adult Mammalian Central Nervous System. Science 1992, 255, 1707–1710. https://doi.org/10.1126/SCIENCE.1553558.
Yuan, X.; Curtin, J.; Xiong, Y.; Liu, G.; Waschsmann-Hogiu, S.; Farkas, D.L.; Black, K.L.; Yu, J.S. Isolation of Cancer Stem Cells from Adult Glioblastoma Multiforme. Oncogene 2004, 23, 9392–9400. https://doi.org/10.1038/SJ.ONC.1208311.
Walcher, L.; Kistenmacher, A.K.; Suo, H.; Kitte, R.; Dluczek, S.; Strauß, A.; Blaudszun, A.R.; Yevsa, T.; Fricke, S.; Kossatz-Boehlert, U. Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Front. Immunol. 2020, 11,1280. https://doi.org/10.3389/FIMMU.2020.01280.
Singh, S.K.; Clarke, I.D.; Terasaki, M.; Bonn, V.E.; Hawkins, C.; Squire, J.; Dirks, P.B. Identification of a Cancer Stem Cell in Human Brain Tumors. Cancer Res. 2003, 63, 5821–5828.
Clarke, M.F.; Dick, J.E.; Dirks, P.B.; Eaves, C.J.; Jamieson, C.H.M.; Jones, D.L.; Visvader, J.; Weissman, I.L.; Wahl, G.M. Cancer Stem Cells—Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells. Cancer Res. 2006, 66, 9339–9344. https://doi.org/10.1158/0008-5472.CAN-06-3126.
Hanahan, D.; Weinberg, R.A. The Hallmarks of Cancer. Cell 2000, 100, 57–70. https://doi.org/10.1016/S0092-8674(00)81683-9.
Ricci-Vitiani, L.; Lombardi, D.G.; Pilozzi, E.; Biffoni, M.; Todaro, M.; Peschle, C.; de Maria, R. Identification and Expansion of Human Colon-Cancer-Initiating Cells. Nature 2007, 445, 111–115. https://doi.org/10.1038/NATURE05384.
Rahmathulla, G.; Toms, S.A.; Weil, R.J. The Molecular Biology of Brain Metastasis. J. Oncol. 2012, 2012, 723541. https://doi.org/10.1155/2012/723541.
Collins, A.T.; Berry, P.A.; Hyde, C.; Stower, M.J.; Maitland, N.J. Prospective Identification of Tumorigenic Prostate Cancer Stem Cells. Cancer Res. 2005, 65, 10946–10951. https://doi.org/10.1158/0008-5472.CAN-05-2018.
Dalerba, P.; Dylla, S.J.; Park, I.K.; Liu, R.; Wang, X.; Cho, R.W.; Hoey, T.; Gurney, A.; Huang, E.H.; Simeone, D.M.; et al. Phenotypic Characterization of Human Colorectal Cancer Stem Cells. Proc. Natl. Acad. Sci. USA 2007, 104, 10158–10163. https://doi.org/10.1073/PNAS.0703478104.
O’Brien, C.A.; Pollett, A.; Gallinger, S.; Dick, J.E. A Human Colon Cancer Cell Capable of Initiating Tumour Growth in Immunodeficient Mice. Nature 2007, 445, 106–110. https://doi.org/10.1038/NATURE05372.
Li, C.; Heidt, D.G.; Dalerba, P.; Burant, C.F.; Zhang, L.; Adsay, V.; Wicha, M.; Clarke, M.F.; Simeone, D.M. Identification of Pancreatic Cancer Stem Cells. Cancer Res. 2007, 67, 1030–1037. https://doi.org/10.1158/0008-5472.CAN-06-2030.
Ignatova, T.N.; Kukekov, V.G.; Laywell, E.D.; Suslov, O.N.; Vrionis, F.D.; Steindler, D.A. Human Cortical Glial Tumors Contain Neural Stem-like Cells Expressing Astroglial and Neuronal Markers in vitro. Glia 2002, 39, 193–206. https://doi.org/10.1002/GLIA.10094.
Hemmati, H.D.; Nakano, I.; Lazareff, J.A.; Masterman-Smith, M.; Geschwind, D.H.; Bronner-Fraser, M.; Kornblum, H.I. Cancerous Stem Cells Can Arise from Pediatric Brain Tumors. Proc. Natl. Acad. Sci. USA 2003, 100, 15178–15183. https://doi.org/10.1073/PNAS.2036535100.
Bao, S.; Wu, Q.; McLendon, R.E.; Hao, Y.; Shi, Q.; Hjelmeland, A.B.; Dewhirst, M.W.; Bigner, D.D.; Rich, J.N. Glioma Stem Cells Promote Radioresistance by Preferential Activation of the DNA Damage Response. Nature 2006, 444, 756–760. https://doi.org/10.1038/NATURE05236.
Vermeulen, L.; de Sousa e Melo, F.; Richel, D.J.; Medema, J.P. The Developing Cancer Stem-Cell Model: Clinical Challenges and Opportunities. Lancet Oncol. 2012, 13, e83–e89. https://doi.org/10.1016/S1470-2045(11)70257-1.
Gimple, R.C.; Bhargava, S.; Dixit, D.; Rich, J.N. Glioblastoma Stem Cells: Lessons from the Tumor Hierarchy in a Lethal Cancer. Genes Dev. 2019, 33, 591–609. https://doi.org/10.1101/GAD.324301.119.
Ahmad, Z.; Jasnos, L.; Gil, V.; Howell, L.; Hallsworth, A.; Petrie, K.; Sawado, T.; Chesler, L. Molecular and In Vivo Characterization of Cancer-Propagating Cells Derived from MYCN-Dependent Medulloblastoma. PLoS ONE 2015, 10, e0119834. https://doi.org/10.1371/JOURNAL.PONE.0119834.
Huang, G.H.; Xu, Q.F.; Cui, Y.H.; Li, N.; Bian, X.W.; Lv, S.Q. Medulloblastoma Stem Cells: Promising Targets in Medulloblastoma Therapy. Cancer Sci. 2016, 107, 583–589. https://doi.org/10.1111/CAS.12925.
Bahmad, H.F.; Poppiti, R.J. Medulloblastoma Cancer Stem Cells: Molecular Signatures and Therapeutic Targets. J. Clin. Pathol. 2020, 73, 243–249. https://doi.org/10.1136/JCLINPATH-2019-206246.
Meco, D.; Servidei, T.; Lamorte, G.; Binda, E.; Arena, V.; Riccardi, R. Ependymoma Stem Cells Are Highly Sensitive to Temozolomide in Vitro and in Orthotopic Models. Neuro-Oncology 2014, 16, 1067–1077. https://doi.org/10.1093/NEUONC/NOU008.
Taylor, M.D.; Poppleton, H.; Fuller, C.; Su, X.; Liu, Y.; Jensen, P.; Magdaleno, S.; Dalton, J.; Calabrese, C.; Board, J.; et al. Radial Glia Cells Are Candidate Stem Cells of Ependymoma. Cancer Cell 2005, 8, 323–335. https://doi.org/10.1016/J.CCR.2005.09.001/ATTACHMENT/8A21D33E-EFEA-4AE9-B3C2-D9CAAF019D8E/MMC5.XLS.
Milde, T.; Kleber, S.; Korshunov, A.; Witt, H.; Hielscher, T.; Koch, P.; Kopp, H.G.; Jugold, M.; Deubzer, H.E.; Oehme, I.; et al. A Novel Human High-Risk Ependymoma Stem Cell Model Reveals the Differentiation-Inducing Potential of the Histone Deacetylase Inhibitor Vorinostat. Acta Neuropathol. 2011, 122, 637–650. https://doi.org/10.1007/S00401-011-0866-3/FIGURES/6.
Servidei, T.; Lucchetti, D.; Navarra, P.; Sgambato, A.; Riccardi, R.; Ruggiero, A. Cell-of-Origin and Genetic, Epigenetic, and Microenvironmental Factors Contribute to the Intra-Tumoral Heterogeneity of Pediatric Intracranial Ependymoma. Cancers (Basel) 2021, 13, 6100. https://doi.org/10.3390/CANCERS13236100.
Filbin, M.G.; Tirosh, I.; Hovestadt, V.; Shaw, M.L.; Escalante, L.E.; Mathewson, N.D.; Neftel, C.; Frank, N.; Pelton, K.; Hebert, C.M.; et al. Developmental and Oncogenic Programs in H3K27M Gliomas Dissected by Single-Cell RNA-Seq. Science 2018, 360, 331–335. https://doi.org/10.1126/science.aao4750.
Lathia, J.D.; Mack, S.C.; Mulkearns-Hubert, E.E.; Valentim, C.L.L.; Rich, J.N. Cancer Stem Cells in Glioblastoma. Genes Dev. 2015, 29, 1203–1217. https://doi.org/10.1101/GAD.261982.115.
Glumac, P.M.; LeBeau, A.M. The Role of CD133 in Cancer: A Concise Review. Clin. Transl. Med. 2018, 7, 18. https://doi.org/10.1186/S40169-018-0198-1.
Uchida, N.; Buck, D.W.; He, D.; Reitsma, M.J.; Masek, M.; Phan, T.V.; Tsukamoto, A.S.; Gage, F.H.; Weissman, I.L. Direct Isolation of Human Central Nervous System Stem Cells. Proc. Natl. Acad. Sci. USA 2000, 97, 14720–14725. https://doi.org/10.1073/PNAS.97.26.14720/ASSET/44FF50DF-D3A5-41A6-BC78-7CE23915D1D9/ASSETS/GRAPHIC/PQ2604988005.JPEG.
Sun, Y.; Kong, W.; Falk, A.; Hu, J.; Zhou, L.; Pollard, S.; Smith, A. CD133 (Prominin) Negative Human Neural Stem Cells Are Clonogenic and Tripotent. PLoS ONE 2009, 4, e5498. https://doi.org/10.1371/JOURNAL.PONE.0005498.
Shu, Q.; Wong, K.K.; Su, J.M.; Adesina, A.M.; Yu, L.T.; Tsang, Y.T.M.; Antalffy, B.C.; Baxter, P.; Perlaky, L.; Yang, J.; et al. Direct Orthotopic Transplantation of Fresh Surgical Specimen Preserves CD133+ Tumor Cells in Clinically Relevant Mouse Models of Medulloblastoma and Glioma. Stem Cells 2008, 26, 1414–1424. https://doi.org/10.1634/STEMCELLS.2007-1009.
Baxter, P.A.; Lin, Q.; Mao, H.; Kogiso, M.; Zhao, X.; Liu, Z.; Huang, Y.; Voicu, H.; Gurusiddappa, S.; Su, J.M.; et al. Silencing BMI1 Eliminates Tumor Formation of Pediatric Glioma CD133+ Cells Not by Affecting Known Targets but by Down-Regulating a Novel Set of Core Genes. Acta Neuropathol. Commun. 2014, 2, 160. https://doi.org/10.1186/S40478-014-0160-4.
Thirant, C.; Bessette, B.; Varlet, P.; Puget, S.; Cadusseau, J.; Tavares, S.d.R.; Studler, J.M.; Silvestre, D.C.; Susini, A.; Villa, C.; et al. Clinical Relevance of Tumor Cells with Stem-Like Properties in Pediatric Brain Tumors. PLoS ONE 2011, 6, e16375. https://doi.org/10.1371/JOURNAL.PONE.0016375.
Kumar, S.S.; Sengupta, S.; Lee, K.; Hura, N.; Fuller, C.; DeWire, M.; Stevenson, C.B.; Fouladi, M.; Drissi, R. BMI-1 Is a Potential Therapeutic Target in Diffuse Intrinsic Pontine Glioma. Oncotarget 2017, 8, 62962–62975. https://doi.org/10.18632/ONCOTARGET.18002.
Surowiec, R.K.; Ferris, S.F.; Apfelbaum, A.; Espinoza, C.; Mehta, R.K.; Monchamp, K.; Sirihorachai, V.R.; Bedi, K.; Ljungman, M.; Galban, S. Transcriptomic Analysis of Diffuse Intrinsic Pontine Glioma (DIPG) Identifies a Targetable ALDH-Positive Subset of Highly Tumorigenic Cancer Stem-like Cells. Mol. Cancer Res. 2021, 19, 223–239. https://doi.org/10.1158/1541-7786.MCR-20-0464.
Chen, R.; Nishimura, M.C.; Bumbaca, S.M.; Kharbanda, S.; Forrest, W.F.; Kasman, I.M.; Greve, J.M.; Soriano, R.H.; Gilmour, L.L.; Rivers, C.S.; et al. A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma. Cancer Cell 2010, 17, 362– 375. https://doi.org/10.1016/J.CCR.2009.12.049.
Wang, J.; Sakariassen, P.; Tsinkalovsky, O.; Immervoll, H.; Bøe, S.O.; Svendsen, A.; Prestegarden, L.; Røsland, G.; Thorsen, F.; Stuhr, L.; et al. CD133 Negative Glioma Cells Form Tumors in Nude Rats and Give Rise to CD133 Positive Cells. Int. J. Cancer 2008, 122, 761–768. https://doi.org/10.1002/IJC.23130.
Beier, D.; Hau, P.; Proescholdt, M.; Lohmeier, A.; Wischhusen, J.; Oefner, P.J.; Aigner, L.; Brawanski, A.; Bogdahn, U.; Beier, C.P. CD133(+) and CD133(−) Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles. Cancer Res. 2007, 67, 4010–4015. https://doi.org/10.1158/0008-5472.CAN-06-4180.
Bhattacharya, R.; Banerjee Mustafi, S.; Street, M.; Dey, A.; Dwivedi, S.K.D. Bmi-1: At the Crossroads of Physiological and Pathological Biology. Genes Dis. 2015, 2, 225–239. https://doi.org/10.1016/J.GENDIS.2015.04.001.
Ballester, L.Y.; Wang, Z.; Shandilya, S.; Miettinen, M.; Burger, P.C.; Eberhart, C.G.; Rodriguez, F.J.; Raabe, E.; Nazarian, J.; Warren, K.; et al. Morphologic Characteristics and Immunohistochemical Profile of Diffuse Intrinsic Pontine Gliomas. Am. J. Surg. Pathol. 2013, 37, 1357–1364. https://doi.org/10.1097/PAS.0B013E318294E817.
Kreso, A.; van Galen, P.; Pedley, N.M.; Lima-Fernandes, E.; Frelin, C.; Davis, T.; Cao, L.; Baiazitov, R.; Du, W.; Sydorenko, N.; et al. Self-Renewal as a Therapeutic Target in Human Colorectal Cancer. Nat. Med. 2014, 20, 29–36. https://doi.org/10.1038/NM.3418.
Vassalli, G. Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells. Stem Cells Int. 2019, 2019, 3904645. https://doi.org/10.1155/2019/3904645.
Altevogt, P.; Doberstein, K.; Fogel, M. L1CAM in Human Cancer. Int. J. Cancer 2016, 138, 1565–1576. https://doi.org/10.1002/IJC.29658.
Bao, S.; Wu, Q.; Li, Z.; Sathornsumetee, S.; Wang, H.; McLendon, R.E.; Hjelmeland, A.B.; Rich, J.N. Targeting Cancer Stem Cells through L1CAM Suppresses Glioma Growth. Cancer Res. 2008, 68, 6043. https://doi.org/10.1158/0008-5472.CAN-08-1079.
Glazer, R.I.; Wang, X.Y.; Yuan, H.; Yin, Y. Musashi1: A Stem Cell Marker No Longer in Search of a Function. Cell Cycle 2008, 7, 2635–2639. https://doi.org/10.4161/CC.7.17.6522.
Pötschke, R.; Haase, J.; Glaß, M.; Simmermacher, S.; Misiak, C.; Penalva, L.O.F.; Kühnöl, C.D.; Hüttelmaier, S. MSI1 Promotes the Expression of the GBM Stem Cell Marker CD44 by Impairing MiRNA-Dependent Degradation. Cancers (Basel) 2020, 12, 3654. https://doi.org/10.3390/CANCERS12123654.
Pötschke, R.; Gielen, G.; Pietsch, T.; Kramm, C.; Klusmann, J.H.; Hüttelmaier, S.; Kühnöl, C.D. Musashi1 Enhances Chemotherapy Resistance of Pediatric Glioblastoma Cells in vitro. Pediatric Res. 2020, 87, 669–676. https://doi.org/10.1038/S41390-019-0628-9.
Bernal, A.; Arranz, L. Nestin-Expressing Progenitor Cells: Function, Identity and Therapeutic Implications. Cell. Mol. Life Sci. 2018, 75, 2177–2195. https://doi.org/10.1007/S00018-018-2794-Z.
Qin, E.Y.; Cooper, D.D.; Abbott, K.L.; Vogel, H.; Jackson, P.K.; Correspondence, M.M. Neural Precursor-Derived Pleiotrophin Mediates Subventricular Zone Invasion by Glioma. Cell 2017, 170, 845–849.e19. https://doi.org/10.1016/j.cell.2017.07.016.
Xu, C.; Liu, X.; Geng, Y.; Bai, Q.; Pan, C.; Sun, Y.; Chen, X.; Yu, H.; Wu, Y.; Zhang, P.; et al. Patient-Derived DIPG Cells Preserve Stem-like Characteristics and Generate Orthotopic Tumors. Oncotarget 2017, 8, 76644–76655. https://doi.org/10.18632/ONCOTARGET.19656.
Mamun, M.A.; Mannoor, K.; Cao, J.; Qadri, F.; Song, X. SOX2 in Cancer Stemness: Tumor Malignancy and Therapeutic Potentials. J. Mol. Cell Biol. 2020, 12, 85–98. https://doi.org/10.1093/JMCB/MJY080.
Finlay, J.; Hallou, C.; Dewari, P.; Pollard, S.; Pathania, M.; Bulstrode, H.; Rowitch, D. Characterising a SOX2+ OLIG2+ Glioma Stem Cell Using Crispr-Engineered Fluorescent Reporters in Primary Patient-Derived GBM and DIPG Cells. Neuro-Oncology 2019, 21, iv9. https://doi.org/10.1093/NEUONC/NOZ167.039.
Otero, J.J.; Rowitch, D.; Vandenberg, S. OLIG2 Is Differentially Expressed in Pediatric Astrocytic and in Ependymal Neoplasms. J. Neuro-Oncol. 2011, 104, 423–438. https://doi.org/10.1007/S11060-010-0509-X.
Kosty, J.; Lu, F.; Kupp, R.; Mehta, S.; Lu, Q.R. Harnessing OLIG2 Function in Tumorigenicity and Plasticity to Target Malignant Gliomas. Cell Cycle 2017, 16, 1654–1660. https://doi.org/10.1080/15384101.2017.1361062.
Theunissen, T.W.; Silva, J.C.R. Switching on Pluripotency: A Perspective on the Biological Requirement of Nanog. Philos. Trans. R. Soc. B: Biol. Sci. 2011, 366, 2222–2229. https://doi.org/10.1098/RSTB.2011.0003.
Ye, Y.; Zhang, M.; Yan, G.; Ma, Q.; Yan, Z.; Wang, L.; Yang, K.; Guo, D. Nanog Promotes Stem-like Traits of Glioblastoma Cells. Front. Biosci.-Landmark 2021, 26, 552–565. https://doi.org/10.2741/4907/4907/FIG6.JPG.
Anido, J.; Sáez-Borderías, A.; Gonzàlez-Juncà, A.; Rodón, L.; Folch, G.; Carmona, M.A.; Prieto-Sánchez, R.M.; Barba, I.; Martínez-Sáez, E.; Prudkin, L.; et al. TGF-β Receptor Inhibitors Target the CD44(High)/Id1(High) Glioma-Initiating Cell Population in Human Glioblastoma. Cancer Cell 2010, 18, 655–668. https://doi.org/10.1016/J.CCR.2010.10.023.
Hartheimer, J.S.; Park, S.; Rao, S.S.; Kim, Y. Targeting Hyaluronan Interactions for Glioblastoma Stem Cell Therapy. Cancer Microenviron. 2019, 12, 47–56. https://doi.org/10.1007/S12307-019-00224-2.
Wang, H.H.; Liao, C.C.; Chow, N.H.; Huang, L.L.H.; Chuang, J.I.; Wei, K.C.; Shin, J.W. Whether CD44 Is an Applicable Marker for Glioma Stem Cells. Am. J. Transl. Res. 2017, 9, 4785.
Mooney, K.L.; Choy, W.; Sidhu, S.; Pelargos, P.; Bui, T.T.; Voth, B.; Barnette, N.; Yang, I. The Role of CD44 in Glioblastoma Multiforme. J. Clin. Neurosci. 2016, 34, 1–5. https://doi.org/10.1016/J.JOCN.2016.05.012.
Georgescu, M.M.; Islam, M.Z.; Li, Y.; Circu, M.L.; Traylor, J.; Notarianni, C.M.; Kline, C.N.; Burns, D.K. Global Activation of Oncogenic Pathways Underlies Therapy Resistance in Diffuse Midline Glioma. Acta Neuropathol. Commun. 2020, 8, 111. https://doi.org/10.1186/S40478-020-00992-9/FIGURES/5.
Mount, C.W.; Majzner, R.G.; Sundaresh, S.; Arnold, E.P.; Kadapakkam, M.; Haile, S.; Labanieh, L.; Hulleman, E.; Woo, P.J.; Rietberg, S.P.; et al. Potent Antitumor Efficacy of Anti-GD2 CAR T Cells in H3-K27M+ Diffuse Midline Gliomas Letter. Nat. Med. 2018, 24, 572–579. https://doi.org/10.1038/S41591-018-0006-X.
Hoeman, C.M.; Cordero, F.J.; Hu, G.; Misuraca, K.; Romero, M.M.; Cardona, H.J.; Nazarian, J.; Hashizume, R.; McLendon, R.; Yu, P.; et al. ACVR1 R206H Cooperates with H3.1K27M in Promoting Diffuse Intrinsic Pontine Glioma Pathogenesis. Nat. Commun. 2019, 10, 1023. https://doi.org/10.1038/s41467-019-08823-9.
Hassn Mesrati, M.; Behrooz, A.B.; Abuhamad, A.Y.; Syahir, A. Understanding Glioblastoma Biomarkers: Knocking a Mountain with a Hammer. Cells 2020, 9, 1236. https://doi.org/10.3390/CELLS9051236.
Donovan, L.K.; Potter, N.E.; Warr, T.; Pilkington, G.J. A Prominin-1-Rich Pediatric Glioblastoma: Biologic Behavior Is Determined by Oxygen Tension-Modulated CD133 Expression but Not Accompanied by Underlying Molecular Profiles. Transl. Oncol. 2012, 5, 141–154. https://doi.org/10.1593/TLO.11337.
De, P.C.; Hamer, W.; van Tilborg, A.; Eijk, P.P.; Sminia, P.; Troost, D.; van Noorden, C.; Ylstra, B.; Leenstra, S. The Genomic Profile of Human Malignant Glioma Is Altered Early in Primary Cell Culture and Preserved in Spheroids. Oncogene 2008, 27, 2091–2096. https://doi.org/10.1038/sj.onc.1210850.
Lee, J.; Kotliarova, S.; Kotliarov, Y.; Li, A.; Su, Q.; Donin, N.M.; Pastorino, S.; Purow, B.W.; Christopher, N.; Zhang, W.; et al. Tumor Stem Cells Derived from Glioblastomas Cultured in BFGF and EGF More Closely Mirror the Phenotype and Genotype of Primary Tumors than Do Serum-Cultured Cell Lines. Cancer Cell 2006, 9, 391–403. https://doi.org/10.1016/J.CCR.2006.03.030.
Wenger, A.; Larsson, S.; Danielsson, A.; Elbæk, K.J.; Kettunen, P.; Tisell, M.; Sabel, M.; Lannering, B.; Nordborg, C.; Schepke, E.; et al. Stem Cell Cultures Derived from Pediatric Brain Tumors Accurately Model the Originating Tumors. Oncotarget 2017, 8, 18626–18639. https://doi.org/10.18632/ONCOTARGET.14826.
Larsson, S.; Wenger, A.; Dósa, S.; Sabel, M.; Kling, T.; Carén, H. Cell Line-Based Xenograft Mouse Model of Paediatric Glioma Stem Cells Mirrors the Clinical Course of the Patient. Carcinogenesis 2018, 39, 1304–1309. https://doi.org/10.1093/CARCIN/BGY091.
He, C.; Xu, K.; Zhu, X.; Dunphy, P.S.; Gudenas, B.; Lin, W.; Twarog, N.; Hover, L.D.; Kwon, C.H.; Kasper, L.H.; et al. Patient-Derived Models Recapitulate Heterogeneity of Molecular Signatures and Drug Response in Pediatric High-Grade Glioma. Nat. Commun. 2021, 12, 4089. https://doi.org/10.1038/S41467-021-24168-8.
Furusawa, C.; Kaneko, K. Chaotic Expression Dynamics Implies Pluripotency: When Theory and Experiment Meet. Biol. Direct 2009, 4, 17. https://doi.org/10.1186/1745-6150-4-17.
Lan, X.; Jörg, D.J.; Cavalli, F.M.G.; Richards, L.M.; Nguyen, L.V.; Vanner, R.J.; Guilhamon, P.; Lee, L.; Kushida, M.M.; Pellacani, D.; et al. Fate Mapping of Human Glioblastoma Reveals an Invariant Stem Cell Hierarchy. Nature 2017, 549, 227–232. https://doi.org/10.1038/NATURE23666.
Tirosh, I.; Venteicher, A.S.; Hebert, C.; Escalante, L.E.; Patel, A.P.; Yizhak, K.; Fisher, J.M.; Rodman, C.; Mount, C.; Filbin, M.G.; et al. Single-Cell RNA-Seq Supports a Developmental Hierarchy in Human Oligodendroglioma. Nature 2016, 539, 309–313. https://doi.org/10.1038/nature20123.
Suvà, M.L.; Tirosh, I. The Glioma Stem Cell Model in the Era of Single-Cell Genomics. Cancer Cell 2020, 37, 630–636. https://doi.org/10.1016/J.CCELL.2020.04.001.
Dirkse, A.; Golebiewska, A.; Buder, T.; Nazarov, P.V.; Muller, A.; Poovathingal, S.; Brons, N.H.C.; Leite, S.; Sauvageot, N.; Sarkisjan, D.; et al. Stem Cell-Associated Heterogeneity in Glioblastoma Results from Intrinsic Tumor Plasticity Shaped by the Microenvironment. Nat. Commun. 2019, 10, 1787. https://doi.org/10.1038/S41467-019-09853-Z.
Hoffman, M.; Gillmor, A.H.; Kunz, D.J.; Johnston, M.J.; Nikolic, A.; Narta, K.; Zarrei, M.; King, J.; Ellestad, K.; Dang, N.H.; et al. Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma. Cancer Res. 2019, 79, 2111–2123. https://doi.org/10.1158/0008-5472.CAN-18-3441.
Franjic, D.; Skarica, M.; Ma, S.; Arellano, J.I.; Tebbenkamp, A.T.N.; Choi, J.; Xu, C.; Li, Q.; Morozov, Y.M.; Andrijevic, D.; et al. Transcriptomic Taxonomy and Neurogenic Trajectories of Adult Human, Macaque, and Pig Hippocampal and Entorhinal Cells. Neuron 2022, 110, 452–469.e14. https://doi.org/10.1016/j.neuron.2021.10.036.
Goffart, N.; Lombard, A.; Lallemand, F.; Kroonen, J.; Nassen, J.; di Valentin, E.; Berendsen, S.; Dedobbeleer, M.; Willems, E.; Robe, P.; et al. CXCL12 Mediates Glioblastoma Resistance to Radiotherapy in the Subventricular Zone. Neuro-Oncology 2017, 19, 66–77. https://doi.org/10.1093/neuonc/now136.
Piccirillo, S.G.M.; Spiteri, I.; Sottoriva, A.; Touloumis, A.; Ber, S.; Price, S.J.; Heywood, R.; Francis, N.J.; Howarth, K.D.; Collins, V.P.; et al. Contributions to Drug Resistance in Glioblastoma Derived from Malignant Cells in the Sub-Ependymal Zone. Cancer Res. 2015, 75, 194–202. https://doi.org/10.1158/0008-5472.CAN-13-3131/651340/AM/CONTRIBUTIONS-TO-DRUG-RESISTANCE-IN-GLIOBLASTOMA.
Baker, S.J.; Ellison, D.W.; Gutmann, D.H. Pediatric Gliomas as Neurodevelopmental Disorders. Glia 2016, 64, 879. https://doi.org/10.1002/GLIA.22945.
Alcantara Llaguno, S.; Chen, J.; Kwon, C.H.; Jackson, E.L.; Li, Y.; Burns, D.K.; Alvarez-Buylla, A.; Parada, L.F. Malignant Astrocytomas Originate from Neural Stem/Progenitor Cells in a Somatic Tumor Suppressor Mouse Model. Cancer Cell 2009, 15, 45–56. https://doi.org/10.1016/J.CCR.2008.12.006.
Lee, J.H.; Lee, J.E.; Kahng, J.Y.; Kim, S.H.; Park, J.S.; Yoon, S.J.; Um, J.-Y.; Kim, W.K.; Lee, J.-K.; Park, J.; et al. Human Glioblastoma Arises from Subventricular Zone Cells with Low-Level Driver Mutations. Nature 2018, 560, 243–247. https://doi.org/10.1038/s41586-018-0389-3.
Wang, Z.; Sun, D.; Chen, Y.J.; Xie, X.; Shi, Y.; Tabar, V.; Brennan, C.W.; Bale, T.A.; Jayewickreme, C.D.; Laks, D.R.; et al. Cell Lineage-Based Stratification for Glioblastoma. Cancer Cell 2020, 38, 366-379.e8. https://doi.org/10.1016/J.CCELL.2020.06.003.
Monje, M.; Mitra, S.S.; Freret, M.E.; Raveh, T.B.; Kim, J.; Masek, M.; Attema, J.L.; Li, G.; Haddix, T.; Edwards, M.S.B.; et al. Hedgehog-Responsive Candidate Cell of Origin for Diffuse Intrinsic Pontine Glioma. Proc. Natl. Acad. Sci. USA 2011, 108, 4453– 4458. https://doi.org/10.1073/pnas.1101657108.
Chen, C.C.L.; Deshmukh, S.; Jessa, S.; Hadjadj, D.; Lisi, V.; Andrade, A.F.; Faury, D.; Jawhar, W.; Dali, R.; Suzuki, H.; et al. Histone H3.3G34-Mutant Interneuron Progenitors Co-Opt PDGFRA for Gliomagenesis. Cell 2020, 183, 1617–1633.e22. https://doi.org/10.1016/j.cell.2020.11.012.
Lombard, A.; Digregorio, M.; Delcamp, C.; Rogister, B.; Piette, C.; Coppieters, N. The Subventricular Zone, a Hideout for Adult and Pediatric High-Grade Glioma Stem Cells. Front. Oncol. 2021, 10, 3197. https://doi.org/10.3389/FONC.2020.614930/BIBTEX.
Caretti, V.; Bugiani, M.; Freret, M.; Schellen, P.; Jansen, M.; van Vuurden, D.; Kaspers, G.; Fisher, P.G.; Hulleman, E.; Wesseling, P.; et al. Subventricular Spread of Diffuse Intrinsic Pontine Glioma. Acta Neuropathol. 2014, 128, 605–607. https://doi.org/10.1007/s00401-014-1307-x.
Mistry, A.M.; Mummareddy, N.; CreveCoeur, T.S.; Lillard, J.C.; Vaughn, B.N.; Gallant, J.-N.; Hale, A.T.; Griffin, N.; Wellons, J.C.; Limbrick, D.D.; et al. Association between Supratentorial Pediatric High-Grade Gliomas Involved with the Subventricular Zone and Decreased Survival: A Multi-Institutional Retrospective Study. J. Neurosurg. Pediatrics 2020, 26, 288–294. https://doi.org/10.3171/2020.3.PEDS19593.
Jalali, R.; Mallick, I.; Dutta, D.; Goswami, S.; Gupta, T.; Munshi, A.; Deshpande, D.; Sarin, R. Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 2010, 77, 974–979. https://doi.org/10.1016/j.ijrobp.2009.06.025.
Khatua, S.; Dhall, G.; O’Neil, S.; Jubran, R.; Villablanca, J.G.; Marachelian, A.; Nastia, A.; Lavey, R.; Olch, A.J.; Gonzalez, I.; et al. Treatment of Primary CNS Germinomatous Germ Cell Tumors with Chemotherapy Prior to Reduced Dose Whole Ventricular and Local Boost Irradiation. Pediatric Blood Cancer 2010, 55, 42–46. https://doi.org/10.1002/pbc.22468.
Biserova, K.; Jakovlevs, A.; Uljanovs, R.; Strumfa, I. Cancer Stem Cells: Significance in Origin, Pathogenesis and Treatment of Glioblastoma. Cells 2021, 10, 621. https://doi.org/10.3390/CELLS10030621.
Skoda, A.M.; Simovic, D.; Karin, V.; Kardum, V.; Vranic, S.; Serman, L. The Role of the Hedgehog Signaling Pathway in Cancer: A Comprehensive Review. Bosn. J. Basic Med. Sci. 2018, 18, 8–20. https://doi.org/10.17305/bjbms.2018.2756.
Lathia, J.D.; Mattson, M.P.; Cheng, A. Notch: From Neural Development to Neurological Disorders. J. Neurochem. 2008, 107, 1471–1481. https://doi.org/10.1111/j.1471-4159.2008.05715.x.
Pierfelice, T.J.; Schreck, K.C.; Eberhart, C.G.; Gaiano, N. Notch, Neural Stem Cells, and Brain Tumors. Cold Spring Harb. Symp. Quant. Biol. 2008, 73, 367–375. https://doi.org/10.1101/sqb.2008.73.013.
Taylor, I.C.; Hütt-Cabezas, M.; Brandt, W.D.; Kambhampati, M.; Nazarian, J.; Chang, H.T.; Warren, K.E.; Eberhart, C.G.; Raabe, E.H. Disrupting NOTCH Slows Diffuse Intrinsic Pontine Glioma Growth, Enhances Radiation Sensitivity, and Shows Combinatorial Efficacy With Bromodomain Inhibition. J. Neuropathol. Exp. Neurol. 2015, 74, 778–790. https://doi.org/10.1097/NEN.0000000000000216.
Madhunapantula, S.V.; Mosca, P.J.; Robertson, G.P. The Akt Signaling Pathway. Cancer Biol. Ther. 2011, 12, 1032–1049. https://doi.org/10.4161/cbt.12.12.18442.
Faury, D.; Nantel, A.; Dunn, S.E.; Guiot, M.-C.; Haque, T.; Hauser, P.; Garami, M.; Bognár, L.; Hanzély, Z.; Liberski, P.P.; et al. Molecular Profiling Identifies Prognostic Subgroups of Pediatric Glioblastoma and Shows Increased YB-1 Expression in Tumors. J. Clin. Oncol. 2007, 25, 1196–1208. https://doi.org/10.1200/JCO.2006.07.8626.
Holland, E.C.; Celestino, J.; Dai, C.; Schaefer, L.; Sawaya, R.E.; Fuller, G.N. Combined Activation of Ras and Akt in Neural Progenitors Induces Glioblastoma Formation in Mice. Nat. Genet. 2000, 25, 55–57. https://doi.org/10.1038/75596.
Mackay, A.; Burford, A.; Carvalho, D.; Izquierdo, E.; Fazal-Salom, J.; Taylor, K.R.; Bjerke, L.; Clarke, M.; Vinci, M.; Nandhabalan, M.; et al. Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma. Cancer Cell 2017, 32, 520–537.e5. https://doi.org/10.1016/J.CCELL.2017.08.017.
Wu, Y.L.; Maachani, U.B.; Schweitzer, M.; Singh, R.; Wang, M.; Chang, R.; Souweidane, M.M. Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor Effects in Diffuse Intrinsic Pontine Glioma Cells. Transl. Oncol. 2017, 10, 221–228. https://doi.org/10.1016/J.TRANON.2016.12.008.
Duchatel, R.; Jackson, E.; Patabendige, A.; Cain, J.; Tsoli, M.; Monje, M.; Alvaro, F.; Ziegler, D.; Dun, M. Dipg-03. Targeting pi3k using the blood brain barrier penetrable inhibitor, gdc-0084, for the treatment of diffuse intrinsic pontine glioma (dipg). Neuro-Oncology 2019, 21, ii68. https://doi.org/10.1093/NEUONC/NOZ036.024.
Chang, R.; Tosi, U.; Voronina, J.; Adeuyan, O.; Wu, L.Y.; Schweitzer, M.E.; Pisapia, D.J.; Becher, O.J.; Souweidane, M.M.; Maachani, U.B. Combined Targeting of PI3K and MEK Effector Pathways via CED for DIPG Therapy. Neurooncol. Adv. 2019, 1, vdz004. https://doi.org/10.1093/NOAJNL/VDZ004.
Gojo, J.; Pavelka, Z.; Zapletalova, D.; Schmook, M.T.; Mayr, L.; Madlener, S.; Kyr, M.; Vejmelkova, K.; Smrcka, M.; Czech, T.; et al. Personalized Treatment of H3K27M-Mutant Pediatric Diffuse Gliomas Provides Improved Therapeutic Opportunities. Front. Oncol. 2020, 9, 1436. https://doi.org/10.3389/FONC.2019.01436/FULL.
Mbah, N.E.; Myers, A.L.; Chung, C.; Thompson, J.K.; Hong, H.S.; Sajjakulnukit, P.; Nwosu, Z.C.; Shan, M.; Sweha, S.R.; Maydan, D.D.; et al. Therapeutic Targeting of Differentiation State-Dependent Metabolic Vulnerabilities in DIPG. bioRxiv 2022, 15, 482555. https://doi.org/10.1101/2022.03.01.482555.
Andtbacka, R.H.; Collichio, F.A.; Amatruda, T.; Senzer, N.; Chesney, J.; Delman, K.; Spitler, L.; Puzanov, I.; Agarwala, S.; Milhem, M.; et al. Final Planned Overall Survival (OS) from OPTiM, a Randomized Phase III Trial of Talimogene Laherparepvec (T-VEC) versus GM-CSF for the Treatment of Unresected Stage IIIB/C/IV Melanoma (NCT00769704). J. ImmunoTherapy Cancer 2014, 2, P263. https://doi.org/10.1186/2051-1426-2-S3-P263.
Markert, J.M.; Razdan, S.N.; Kuo, H.C.; Cantor, A.; Knoll, A.; Karrasch, M.; Nabors, L.B.; Markiewicz, M.; Agee, B.S.; Coleman, J.M.; et al. A Phase 1 Trial of Oncolytic HSV-1, G207, given in Combination with Radiation for Recurrent GBM Demonstrates Safety and Radiographic Responses. Mol. Ther. 2014, 22, 1048–1055. https://doi.org/10.1038/MT.2014.22.
Friedman, G.K.; Langford, C.P.; Coleman, J.M.; Cassady, K.A.; Parker, J.N.; Markert, J.M.; Yancey Gillespie, G. Engineered Herpes Simplex Viruses Efficiently Infect and Kill CD133+ Human Glioma Xenograft Cells That Express CD111. J. Neuro-Oncol. 2009, 95, 199–209. https://doi.org/10.1007/s11060-009-9926-0.
Wakimoto, H.; Kesari, S.; Farrell, C.J.; Curry, W.T.; Zaupa, C.; Aghi, M.; Kuroda, T.; Stemmer-Rachamimov, A.; Shah, K.; Liu, T.C.; et al. Human Glioblastoma-Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors. Cancer Res. 2009, 69, 3472–3481. https://doi.org/10.1158/0008-5472.CAN-08-3886.
Josupeit, R.; Bender, S.; Kern, S.; Leuchs, B.; Hielscher, T.; Herold-Mende, C.; Schlehofer, J.; Dinsart, C.; Witt, O.; Rommelaere, J.; et al. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1. Viruses 2016, 8, 138. https://doi.org/10.3390/v8050138.
Lang, F.F.; Conrad, C.; Gomez-Manzano, C.; Alfred Yung, W.K.; Sawaya, R.; Weinberg, J.S.; Prabhu, S.S.; Rao, G.; Fuller, G.N.; Aldape, K.D.; et al. Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. J. Clin. Oncol. 2018, 36, 1419. https://doi.org/10.1200/JCO.2017.75.8219.
Cobb, D.A.; de Rossi, J.; Liu, L.; An, E.; Lee, D.W. Targeting of the Alpha v Beta 3 Integrin Complex by CAR-T Cells Leads to Rapid Regression of Diffuse Intrinsic Pontine Glioma and Glioblastoma. J. ImmunoTherapy Cancer 2022, 10, e003816. https://doi.org/10.1136/JITC-2021-003816.
Martínez-Vélez, N.; Garcia-Moure, M.; Marigil, M.; González-Huarriz, M.; Puigdelloses, M.; Gallego Pérez-Larraya, J.; Zalacaín, M.; Marrodán, L.; Varela-Guruceaga, M.; Laspidea, V.; et al. The Oncolytic Virus Delta-24-RGD Elicits an Antitumor Effect in Pediatric Glioma and DIPG Mouse Models. Nat. Commun. 2019, 10, 2235. https://doi.org/10.1038/s41467-019-10043-0.
Li, J.; Meng, Q.; Zhou, X.; Zhao, H.; Wang, K.; Niu, H.; Wang, Y. Gospel of Malignant Glioma: Oncolytic Virus Therapy. Gene 2022, 818, 146217. https://doi.org/10.1016/J.GENE.2022.146217.
Wang, Z.; Guo, X.; Gao, L.; Wang, Y.; Guo, Y.; Xing, B.; Ma, W. Classification of Pediatric Gliomas Based on Immunological Profiling: Implications for Immunotherapy Strategies. Mol. Ther. Oncolytics 2021, 20, 34. https://doi.org/10.1016/J.OMTO.2020.12.012.
Friedman, G.K.; Johnston, J.M.; Bag, A.K.; Bernstock, J.D.; Li, R.; Aban, I.; Kachurak, K.; Nan, L.; Kang, K.-D.; Totsch, S.; et al. Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas. N. Engl. J. Med. 2021, 384, 1613–1622. https://doi.org/10.1056/NEJMOA2024947/SUPPL_FILE/NEJMOA2024947_DATA-SHARING.PDF.
Chastkofsky, M.I.; Pituch, K.C.; Katagi, H.; Zannikou, M.; Ilut, L.; Xiao, T.; Han, Y.; Sonabend, A.M.; Curiel, D.T.; Bonner, E.R.; et al. Mesenchymal Stem Cells Successfully Deliver Oncolytic Virotherapy to Diffuse Intrinsic Pontine Glioma. Clin. Cancer Res. 2021, 27, 1766–1777. https://doi.org/10.1158/1078-0432.CCR-20-1499.