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. 2020 Jul 6;3(1):67–90. doi: 10.1089/nsm.2020.0004

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© Blandine Comte et al. 2020; Published by Mary Ann Liebert, Inc.

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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FIG. 4. — The proposed implementation of logical model predictions and patient-derived spheroid testing of drug therapies. An individual patient's tumor material (top row) is used to produce spheroid cultures for small-scale drug combination screening. In parallel, biomarkers are produced from these spheroids (bottom row) and used to configure a generic logical model so that it optimally represents the tumor of the patient. This model is used for a large-scale in silico screening of the complete available drug combination space, resulting in a limited set of potential synergistic drugs that are tested in the spheroids. This whole procedure can be completed in a couple of weeks. Validated drug combinations can be considered by a clinician for therapy decisions.