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Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy

While glioblastoma multiforme (GBM) is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas...

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Autores principales: Friedman, Gregory K., Raborn, Joel, Kelly, Virginia M., Cassady, Kevin A., Markert, James M., Gillespie, G. Yancey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584319/
https://www.ncbi.nlm.nih.gov/pubmed/23450706
http://dx.doi.org/10.3389/fonc.2013.00028
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author Friedman, Gregory K.
Raborn, Joel
Kelly, Virginia M.
Cassady, Kevin A.
Markert, James M.
Gillespie, G. Yancey
author_facet Friedman, Gregory K.
Raborn, Joel
Kelly, Virginia M.
Cassady, Kevin A.
Markert, James M.
Gillespie, G. Yancey
author_sort Friedman, Gregory K.
collection PubMed
description While glioblastoma multiforme (GBM) is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs) remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy and radiotherapy resistant cells, termed “glioma stem cells” (GSCs), “glioma progenitor cells,” or “glioma-initiating cells,” which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGG must be able to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses (oHSV), genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oHSV.
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spelling pubmed-35843192013-02-28 Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy Friedman, Gregory K. Raborn, Joel Kelly, Virginia M. Cassady, Kevin A. Markert, James M. Gillespie, G. Yancey Front Oncol Oncology While glioblastoma multiforme (GBM) is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs) remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy and radiotherapy resistant cells, termed “glioma stem cells” (GSCs), “glioma progenitor cells,” or “glioma-initiating cells,” which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGG must be able to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses (oHSV), genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oHSV. Frontiers Media S.A. 2013-02-28 /pmc/articles/PMC3584319/ /pubmed/23450706 http://dx.doi.org/10.3389/fonc.2013.00028 Text en Copyright © Friedman, Raborn, Kelly, Cassady, Markert and Gillespie. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Oncology
Friedman, Gregory K.
Raborn, Joel
Kelly, Virginia M.
Cassady, Kevin A.
Markert, James M.
Gillespie, G. Yancey
Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy
title Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy
title_full Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy
title_fullStr Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy
title_full_unstemmed Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy
title_short Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy
title_sort pediatric glioma stem cells: biologic strategies for oncolytic hsv virotherapy
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584319/
https://www.ncbi.nlm.nih.gov/pubmed/23450706
http://dx.doi.org/10.3389/fonc.2013.00028
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