The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.

Autor:	Furst LM; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.; Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia., Roussel EM; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.; Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia., Leung RF; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.; Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia., George AM; Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia., Best SA; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3010, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia., Whittle JR; Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.; Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3010, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia., Firestein R; Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia.; Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia., Faux MC; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.; Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.; Department of Surgery, University of Melbourne, Parkville, VIC 3010, Australia., Eisenstat DD; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.; Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.; Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.; Children's Cancer Centre, The Royal Children's Hospital Melbourne, 50 Flemington Road, Parkville, VIC 3052, Australia.
Jazyk:	angličtina
Zdroj:	Biology [Biology (Basel)] 2024 Jun 07; Vol. 13 (6). Date of Electronic Publication: 2024 Jun 07.
DOI:	10.3390/biology13060424
Abstrakt:	Pediatric high-grade gliomas (pHGG) are malignant and usually fatal central nervous system (CNS) WHO Grade 4 tumors. The majority of pHGG consist of diffuse midline gliomas (DMG), H3.3 or H3.1 K27 altered, or diffuse hemispheric gliomas (DHG) (H3.3 G34-mutant). Due to diffuse tumor infiltration of eloquent brain areas, especially for DMG, surgery has often been limited and chemotherapy has not been effective, leaving fractionated radiation to the involved field as the current standard of care. pHGG has only been classified as molecularly distinct from adult HGG since 2012 through Next-Generation sequencing approaches, which have shown pHGG to be epigenetically regulated and specific tumor sub-types to be representative of dysregulated differentiating cells. To translate discovery research into novel therapies, improved pre-clinical models that more adequately represent the tumor biology of pHGG are required. This review will summarize the molecular characteristics of different pHGG sub-types, with a specific focus on histone K27M mutations and the dysregulated gene expression profiles arising from these mutations. Current and emerging pre-clinical models for pHGG will be discussed, including commonly used patient-derived cell lines and in vivo modeling techniques, encompassing patient-derived xenograft murine models and genetically engineered mouse models (GEMMs). Lastly, emerging techniques to model CNS tumors within a human brain environment using brain organoids through co-culture will be explored. As models that more reliably represent pHGG continue to be developed, targetable biological and genetic vulnerabilities in the disease will be more rapidly identified, leading to better treatments and improved clinical outcomes.
Databáze:	MEDLINE
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