@article{d6bb98b487ca47f9b1b09163b1c29688,
title = "Acquired Temozolomide Resistance Instructs Patterns of Glioblastoma Behavior in Gelatin Hydrogels",
abstract = "Acquired drug resistance in glioblastoma (GBM) presents a major clinical challenge and is a key factor contributing to abysmal prognosis, with less than 15 months median overall survival. Aggressive chemotherapy with the frontline therapeutic, temozolomide (TMZ), ultimately fails to kill residual highly invasive tumor cells after surgical resection and radiotherapy. Here, a 3D engineered model of acquired TMZ resistance is reported using two isogenically matched sets of GBM cell lines encapsulated in gelatin methacrylol hydrogels. Response of TMZ-resistant versus TMZ-sensitive GBM cell lines within the gelatin-based extracellular matrix platform is benchmarked and drug response at physiologically relevant TMZ concentrations is further validated. The changes in drug sensitivity, cell invasion, and matrix-remodeling cytokine production are shown as the result of acquired TMZ resistance. This platform lays the foundation for future investigations targeting key elements of the GBM tumor microenvironment to combat GBM's devastating impact by advancing the understanding of GBM progression and treatment response to guide the development of novel treatment strategies.",
keywords = "cancer models, drug resistance, glioblastoma, hydrogel",
author = "Kriuchkovskaia, {Victoria A.} and Eames, {Ela K.} and Riggins, {Rebecca B.} and Harley, {Brendan A. C.}",
note = "The authors acknowledge funding from the National Cancer Institute of the National Institutes of Health under Award Number R01 CA256481 (BACH) and R01 CA279195 (R.B.R.) as well as the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number T32 EB019944 (V.K.). The content herein is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors gratefully acknowledge additional funding provided by the Department of Chemical & Biomolecular Engineering and Cancer Center at Illinois at the University of Illinois at Urbana-Champaign. The authors would like to thank Sydney Anne McKee (UIUC) for technical guidance that aided in experimental design and execution. The authors also acknowledge additional funding provided by the Department of Chemical and Biomolecular Engineering, the Carl R. Woese Institute for Genomic Biology, and the Cancer Center at Illinois at the University of Illinois Urbana-Champaign. The authors acknowledge funding from the National Cancer Institute of the National Institutes of Health under Award Number R01 CA256481 (BACH) and R01 CA279195 (R.B.R.) as well as the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number T32 EB019944 (V.K.). The content herein is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors gratefully acknowledge additional funding provided by the Department of Chemical & Biomolecular Engineering and Cancer Center at Illinois at the University of Illinois at Urbana\u2010Champaign. The authors would like to thank Sydney Anne McKee (UIUC) for technical guidance that aided in experimental design and execution. The authors also acknowledge additional funding provided by the Department of Chemical and Biomolecular Engineering, the Carl R. Woese Institute for Genomic Biology, and the Cancer Center at Illinois at the University of Illinois Urbana\u2010Champaign.",
year = "2024",
month = oct,
day = "28",
doi = "10.1002/adhm.202400779",
language = "English (US)",
volume = "13",
journal = "Advanced Healthcare Materials",
issn = "2192-2640",
publisher = "John Wiley & Sons, Ltd.",
number = "27",
}