Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review

Glioblastoma (GBM) remains incurable despite the overwhelming discovery of 2-dimensional (2D) cell-based potential therapeutics since the majority of them have met unsatisfactory results in animal and clinical settings. Incremental empirical evidence has laid the widespread need of transitioning 2D...

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Autores principales:	Brandon Wee Siang Phon, Muhamad N.A. Kamarudin, Saatheeyavaane Bhuvanendran, Ammu K. Radhakrishnan
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	3D Culture Glioblastoma Biodegradable and non-biodegradable scaffolds GBM Motility Drug resistance metabolism Stemness Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/22078187bebb4e2f852bcf6562545ce0
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spelling	oai:doaj.org-article:22078187bebb4e2f852bcf6562545ce02021-11-12T04:25:32ZTransitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review0753-332210.1016/j.biopha.2021.112396https://doaj.org/article/22078187bebb4e2f852bcf6562545ce02022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011823https://doaj.org/toc/0753-3322Glioblastoma (GBM) remains incurable despite the overwhelming discovery of 2-dimensional (2D) cell-based potential therapeutics since the majority of them have met unsatisfactory results in animal and clinical settings. Incremental empirical evidence has laid the widespread need of transitioning 2D to 3-dimensional (3D) cultures that better mimic GBM’s complex and heterogenic nature to allow better translation of pre-clinical results. This systematic scoping review analyses the transcriptomic data involving 3D models of GBM against 2D models from 22 studies identified from four databases (PubMed, ScienceDirect, Medline, and Embase). From a total of 499 genes reported in these studies, 313 (63%) genes were upregulated across 3D models cultured using different scaffolds. Our analysis showed that 4 of the replicable upregulated genes are associated with GBM stemness, epithelial to mesenchymal transition (EMT), hypoxia, and migration-related genes regardless of the type of scaffolds, displaying close resemblances to primitive undifferentiated tumour phenotypes that are associated with decreased overall survival and increased hazard ratio in GBM patients. The upregulation of drug response and drug efflux genes (e.g. cytochrome P450s and ABC transporters) mirrors the GBM genetic landscape that contributes to in vivo and clinical treatment resistance. These upregulated genes displayed strong protein-protein interactions when analysed using an online bioinformatics software (STRING). These findings reinforce the need for widespread transition to 3D GBM models as a relatively inexpensive humanised pre-clinical tool with suitable genetic biomarkers to bridge clinical gaps in potential therapeutic evaluations.Brandon Wee Siang PhonMuhamad N.A. KamarudinSaatheeyavaane BhuvanendranAmmu K. RadhakrishnanElsevierarticle3D CultureGlioblastomaBiodegradable and non-biodegradable scaffoldsGBM MotilityDrug resistance metabolismStemnessTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112396- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	3D Culture Glioblastoma Biodegradable and non-biodegradable scaffolds GBM Motility Drug resistance metabolism Stemness Therapeutics. Pharmacology RM1-950
spellingShingle	3D Culture Glioblastoma Biodegradable and non-biodegradable scaffolds GBM Motility Drug resistance metabolism Stemness Therapeutics. Pharmacology RM1-950 Brandon Wee Siang Phon Muhamad N.A. Kamarudin Saatheeyavaane Bhuvanendran Ammu K. Radhakrishnan Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review
description	Glioblastoma (GBM) remains incurable despite the overwhelming discovery of 2-dimensional (2D) cell-based potential therapeutics since the majority of them have met unsatisfactory results in animal and clinical settings. Incremental empirical evidence has laid the widespread need of transitioning 2D to 3-dimensional (3D) cultures that better mimic GBM’s complex and heterogenic nature to allow better translation of pre-clinical results. This systematic scoping review analyses the transcriptomic data involving 3D models of GBM against 2D models from 22 studies identified from four databases (PubMed, ScienceDirect, Medline, and Embase). From a total of 499 genes reported in these studies, 313 (63%) genes were upregulated across 3D models cultured using different scaffolds. Our analysis showed that 4 of the replicable upregulated genes are associated with GBM stemness, epithelial to mesenchymal transition (EMT), hypoxia, and migration-related genes regardless of the type of scaffolds, displaying close resemblances to primitive undifferentiated tumour phenotypes that are associated with decreased overall survival and increased hazard ratio in GBM patients. The upregulation of drug response and drug efflux genes (e.g. cytochrome P450s and ABC transporters) mirrors the GBM genetic landscape that contributes to in vivo and clinical treatment resistance. These upregulated genes displayed strong protein-protein interactions when analysed using an online bioinformatics software (STRING). These findings reinforce the need for widespread transition to 3D GBM models as a relatively inexpensive humanised pre-clinical tool with suitable genetic biomarkers to bridge clinical gaps in potential therapeutic evaluations.
format	article
author	Brandon Wee Siang Phon Muhamad N.A. Kamarudin Saatheeyavaane Bhuvanendran Ammu K. Radhakrishnan
author_facet	Brandon Wee Siang Phon Muhamad N.A. Kamarudin Saatheeyavaane Bhuvanendran Ammu K. Radhakrishnan
author_sort	Brandon Wee Siang Phon
title	Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review
title_short	Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review
title_full	Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review
title_fullStr	Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review
title_full_unstemmed	Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review
title_sort	transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3d cell-based models: a systematic scoping review
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/22078187bebb4e2f852bcf6562545ce0
work_keys_str_mv	AT brandonweesiangphon transitioningpreclinicalglioblastomamodelstoclinicalsettingswithbiomarkersidentifiedin3dcellbasedmodelsasystematicscopingreview AT muhamadnakamarudin transitioningpreclinicalglioblastomamodelstoclinicalsettingswithbiomarkersidentifiedin3dcellbasedmodelsasystematicscopingreview AT saatheeyavaanebhuvanendran transitioningpreclinicalglioblastomamodelstoclinicalsettingswithbiomarkersidentifiedin3dcellbasedmodelsasystematicscopingreview AT ammukradhakrishnan transitioningpreclinicalglioblastomamodelstoclinicalsettingswithbiomarkersidentifiedin3dcellbasedmodelsasystematicscopingreview
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Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review

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