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This article proposes a new quantitative systems pharmacology (QSP)\u2010based methodology in which cell viability assays are used to calibrate virtual tumors (VTs) made of virtual cells whose fate is determined by simulations from an apoptosis QSP model. VTs representing SU\u2010DHL\u20104 and KARPAS\u2010422 cell lines were calibrated using in\u00a0vitro data involving venetoclax (anti\u2010BCL2), A\u20101155463 (anti\u2010BCLXL), and\/or A\u20101210477 (anti\u2010MCL1). The calibrated VTs provide insights into the combination of several BH3\u2010mimetics, such as the distinction between cells eliminated by at least one of the drugs (monotherapies) from the cells eliminated by a pharmacological combination only. Calibrated VTs can also be used as initial conditions in an agent\u2010based model (ABM) framework, and a minimal ABM was developed to bridge in\u00a0vitro SU\u2010DHL\u20104 cell viability results to tumor growth inhibition experiments in mice.<\/jats:p>","DOI":"10.1002\/psp4.13158","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T14:00:35Z","timestamp":1715781635000},"page":"1252-1263","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quantitative systems pharmacology modeling of tumor heterogeneity in response to <scp>BH3<\/scp>\u2010mimetics using virtual tumors calibrated with cell viability assays"],"prefix":"10.1002","volume":"13","author":[{"given":"Thibaud","family":"Derippe","sequence":"first","affiliation":[{"name":"Institut de Recherches Internationales Servier  Suresnes France"},{"name":"Inserm, UMRS\u20101144, Optimisation Th\u00e9rapeutique en 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