{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:27:52Z","timestamp":1788492472412,"version":"build-2803163510"},"reference-count":22,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007771","name":"Medical University of Silesia","doi-asserted-by":"publisher","award":["BNW-2-054\/N\/5\/F"],"award-info":[{"award-number":["BNW-2-054\/N\/5\/F"]}],"id":[{"id":"10.13039\/100007771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>(1) Background: Caffeic acid phenethyl ester (CAPE) exhibits anticancer activity; however, its time-dependent effects on interconnected signalling pathways remain incompletely characterised. (2) Methods: We combined wet-lab experiments (MTT viability assay and ELISA measurements of total NF\u2212\u03baB p65 and p53) with a Bayesian digital twin framework to quantify signalling dynamics in prostate cancer cells following CAPE exposure. p53-deficient PC3 and p53-competent LNCaP cell lines were treated for 24 h and 48 h across multiple CAPE concentrations. Experimental data were integrated into a mechanistic Bayesian model using robust likelihoods, enabling uncertainty-aware parameter inference and posterior predictive validation via leave-one-dose-out analysis. (3) Results: In PC3 cells, CAPE induced dose-dependent inhibition of NF\u2212\u03baB p65 that was consistently associated with reduced cell viability at both time points, consistent with a p53-independent regulatory regime. In contrast, LNCaP cells exhibited a transient NF\u2212\u03baB\u2013p53 coupling at 24 h, characterised by delayed NF\u2212\u03baB suppression and pronounced p53 activation, followed by a more stable and weakly coupled signalling state at 48 h. These temporal patterns were supported by posterior parameter estimates and predictive performance under leave-one-dose-out validation. (4) Conclusions: This study demonstrates that Bayesian digital twins enable quantitative, uncertainty-aware analysis of time-dependent drug responses, extending beyond conventional dose\u2013response assessments and supporting mechanistic hypothesis generation in cancer pharmacology.<\/jats:p>","DOI":"10.3390\/molecules31040624","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:45:36Z","timestamp":1770831936000},"page":"624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Uncovering Time-Dependent NF \u2212 \u03baB-p53 Crosstalk Induced by Caffeic Acid Phenethyl Ester in Prostate Cancer Cells Through a Bayesian Digital Twin"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6289-7234","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Dzik","sequence":"first","affiliation":[{"name":"Department of Clinical Engineering, Academy of Silesia, ul. Rolna 43, 40-555 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3561-8684","authenticated-orcid":false,"given":"Mateusz","family":"Niedoba","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Ostrog\u00f3rska 30, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3617-3948","authenticated-orcid":false,"given":"Agnieszka","family":"Bregu\u0142a","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Ostrog\u00f3rska 30, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9363-4595","authenticated-orcid":false,"given":"Joanna","family":"Chwa\u0142","sequence":"additional","affiliation":[{"name":"Department of Clinical Engineering, Academy of Silesia, ul. Rolna 43, 40-555 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2580-7954","authenticated-orcid":false,"given":"Ewaryst J.","family":"Tkacz","sequence":"additional","affiliation":[{"name":"Department of Clinical Engineering, Academy of Silesia, ul. Rolna 43, 40-555 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3575-8159","authenticated-orcid":false,"given":"Agata","family":"Kaba\u0142a-Dzik","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Ostrog\u00f3rska 30, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, X., and Jiang, H. (2025). 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