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Article

A Drug Screening Pipeline Using 2D and 3D Patient-Derived In Vitro Models for Pre-Clinical Analysis of Therapy Response in Glioblastoma

1
Centre for Cancer Biology, SA Pathology and the University of South of Australia, Adelaide, SA 5000, Australia
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Adelaide Medical School, University of Adelaide, Adelaide, SA 5000, Australia
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Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
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Flinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Adelaide, SA 5042, Australia
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Department of Neurosurgery, Flinders Medical Centre, Adelaide, SA 5042, Australia
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Cell and Molecular Biology Department, Sid Faithfull Brain Cancer Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
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Faculty of Health, Queensland University of Technology, Brisbane, QLD 4006, Australia
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Faculty of Medicine, University of Queensland, Brisbane, QLD 4072, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Cristina Peña
Int. J. Mol. Sci. 2021, 22(9), 4322; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094322
Received: 29 March 2021 / Revised: 16 April 2021 / Accepted: 19 April 2021 / Published: 21 April 2021
Glioblastoma is one of the most common and lethal types of primary brain tumor. Despite aggressive treatment with chemotherapy and radiotherapy, tumor recurrence within 6–9 months is common. To overcome this, more effective therapies targeting cancer cell stemness, invasion, metabolism, cell death resistance and the interactions of tumor cells with their surrounding microenvironment are required. In this study, we performed a systematic review of the molecular mechanisms that drive glioblastoma progression, which led to the identification of 65 drugs/inhibitors that we screened for their efficacy to kill patient-derived glioma stem cells in two dimensional (2D) cultures and patient-derived three dimensional (3D) glioblastoma explant organoids (GBOs). From the screening, we found a group of drugs that presented different selectivity on different patient-derived in vitro models. Moreover, we found that Costunolide, a TERT inhibitor, was effective in reducing the cell viability in vitro of both primary tumor models as well as tumor models pre-treated with chemotherapy and radiotherapy. These results present a novel workflow for screening a relatively large groups of drugs, whose results could lead to the identification of more personalized and effective treatment for recurrent glioblastoma. View Full-Text
Keywords: glioblastoma; organoids; personalized medicine; therapy resistance; drug screening; tumor microenvironment glioblastoma; organoids; personalized medicine; therapy resistance; drug screening; tumor microenvironment
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MDPI and ACS Style

Lenin, S.; Ponthier, E.; Scheer, K.G.; Yeo, E.C.F.; Tea, M.N.; Ebert, L.M.; Oksdath Mansilla, M.; Poonnoose, S.; Baumgartner, U.; Day, B.W.; Ormsby, R.J.; Pitson, S.M.; Gomez, G.A. A Drug Screening Pipeline Using 2D and 3D Patient-Derived In Vitro Models for Pre-Clinical Analysis of Therapy Response in Glioblastoma. Int. J. Mol. Sci. 2021, 22, 4322. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094322

AMA Style

Lenin S, Ponthier E, Scheer KG, Yeo ECF, Tea MN, Ebert LM, Oksdath Mansilla M, Poonnoose S, Baumgartner U, Day BW, Ormsby RJ, Pitson SM, Gomez GA. A Drug Screening Pipeline Using 2D and 3D Patient-Derived In Vitro Models for Pre-Clinical Analysis of Therapy Response in Glioblastoma. International Journal of Molecular Sciences. 2021; 22(9):4322. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094322

Chicago/Turabian Style

Lenin, Sakthi, Elise Ponthier, Kaitlin G. Scheer, Erica C.F. Yeo, Melinda N. Tea, Lisa M. Ebert, Mariana Oksdath Mansilla, Santosh Poonnoose, Ulrich Baumgartner, Bryan W. Day, Rebecca J. Ormsby, Stuart M. Pitson, and Guillermo A. Gomez 2021. "A Drug Screening Pipeline Using 2D and 3D Patient-Derived In Vitro Models for Pre-Clinical Analysis of Therapy Response in Glioblastoma" International Journal of Molecular Sciences 22, no. 9: 4322. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094322

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