Longitudinal drug synergy assessment using convolutional neural network image-decoding of glioblastoma single-spheroid cultures.

Autor:	Giczewska A; Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland., Pastuszak K; Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.; Center of Biostatistics and Bioinformatics, Medical University of Gdańsk, Gdańsk, Poland.; Department of Algorithms and System Modeling, Gdansk University of Technology, Gdańsk, Poland., Houweling M; Department of Neurosurgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; The WINDOW Consortium (www.window-consortium.org)., Abdul KU; Department of Neurosurgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; The WINDOW Consortium (www.window-consortium.org)., Faaij N; Department of Neurosurgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Wedekind L; Department of Neurosurgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Noske D; Department of Neurosurgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Wurdinger T; Department of Neurosurgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; The WINDOW Consortium (www.window-consortium.org)., Supernat A; Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.; Center of Biostatistics and Bioinformatics, Medical University of Gdańsk, Gdańsk, Poland., Westerman BA; Department of Neurosurgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Cancer Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; The WINDOW Consortium (www.window-consortium.org).
Jazyk:	angličtina
Zdroj:	Neuro-oncology advances [Neurooncol Adv] 2023 Nov 05; Vol. 5 (1), pp. vdad134. Date of Electronic Publication: 2023 Nov 05 (Print Publication: 2023).
DOI:	10.1093/noajnl/vdad134
Abstrakt:	Background: In recent years, drug combinations have become increasingly popular to improve therapeutic outcomes in various diseases, including difficult to cure cancers such as the brain cancer glioblastoma. Assessing the interaction between drugs over time is critical for predicting drug combination effectiveness and minimizing the risk of therapy resistance. However, as viability readouts of drug combination experiments are commonly performed as an endpoint where cells are lysed, longitudinal drug-interaction monitoring is currently only possible through combined endpoint assays. Methods: We provide a method for massive parallel monitoring of drug interactions for 16 drug combinations in 3 glioblastoma models over a time frame of 18 days. In our assay, viabilities of single neurospheres are to be estimated based on image information taken at different time points. Neurosphere images taken on the final day (day 18) were matched to the respective viability measured by CellTiter-Glo 3D on the same day. This allowed to use of machine learning to decode image information to viability values on day 18 as well as for the earlier time points (on days 8, 11, and 15). Results: Our study shows that neurosphere images allow us to predict cell viability from extrapolated viabilities. This enables to assess of the drug interactions in a time window of 18 days. Our results show a clear and persistent synergistic interaction for several drug combinations over time. Conclusions: Our method facilitates longitudinal drug-interaction assessment, providing new insights into the temporal-dynamic effects of drug combinations in 3D neurospheres which can help to identify more effective therapies against glioblastoma. Competing Interests: TW is a shareholder of Illumina, Pacific Biosciences, and Oxford Nanopore. B.W. receives a public–private partnership fund from Health~Holland on a peer-reviewed project where IOTA Pharmaceuticals Ltd and NTRC Therapeutics B.V. are the private parties and contributors to the project. All other authors none declared. (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
Databáze:	MEDLINE
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