Bioengineered Models to Study Microenvironmental Regulation of Glioblastoma Metabolism.
Bioengineered platforms
Biomimetics
Cancer metabolism
Glioblastoma
Mathematical modeling
Microphysiological platforms
Tumor microenvironment
Journal
Journal of neuropathology and experimental neurology
ISSN: 1554-6578
Titre abrégé: J Neuropathol Exp Neurol
Pays: England
ID NLM: 2985192R
Informations de publication
Date de publication:
19 11 2021
19 11 2021
Historique:
entrez:
15
9
2021
pubmed:
16
9
2021
medline:
26
2
2022
Statut:
ppublish
Résumé
Despite extensive research and aggressive therapies, glioblastoma (GBM) remains a central nervous system malignancy with poor prognosis. The varied histopathology of GBM suggests a landscape of differing microenvironments and clonal expansions, which may influence metabolism, driving tumor progression. Indeed, GBM metabolic plasticity in response to differing nutrient supply within these microenvironments has emerged as a key driver of aggressiveness. Additionally, emergent biophysical and biochemical interactions in the tumor microenvironment (TME) are offering new perspectives on GBM metabolism. Perivascular and hypoxic niches exert crucial roles in tumor maintenance and progression, facilitating metabolic relationships between stromal and tumor cells. Alterations in extracellular matrix and its biophysical characteristics, such as rigidity and topography, regulate GBM metabolism through mechanotransductive mechanisms. This review highlights insights gained from deployment of bioengineering models, including engineered cell culture and mathematical models, to study the microenvironmental regulation of GBM metabolism. Bioengineered approaches building upon histopathology measurements may uncover potential therapeutic strategies that target both TME-dependent mechanotransductive and biomolecular drivers of metabolism to tackle this challenging disease. Longer term, a concerted effort integrating in vitro and in silico models predictive of patient therapy response may offer a powerful advance toward tailoring of treatment to patient-specific GBM characteristics.
Identifiants
pubmed: 34524448
pii: 6370675
doi: 10.1093/jnen/nlab092
pmc: PMC9432143
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1012–1023Subventions
Organisme : NINDS NIH HHS
ID : R01 NS062184
Pays : United States
Informations de copyright
© 2021 American Association of Neuropathologists, Inc. All rights reserved.
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