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Here, a bottom\u2010up biomaterial\u2010based platform is introduced to program cell state changes in pancreatic cancer organoids by tuning minimal adhesion cues within a synthetic matrix. A Design of Experiments framework is used to systematically model the patient\u2010specific transcriptome\u2010wide impact of matrix\u2010presented adhesion cues. Focusing on epithelial\u2010mesenchymal transition (EMT) as a proof\u2010of\u2010concept cellular program, a multiobjective optimization approach is applied to identify patient\u2010specific matrix compositions that enrich EMT\u2010associated transcriptional programs. Organoids cultured in these optimized matrices exhibit transcriptomic signatures consistent with EMT enrichment and coordinated shift in EMT\u2010associated regulatory signatures. Secretome profiling further reveals changes in cytokines previously linked to EMT\u2010associated inflammatory, hypoxia, and TGF\u2010\u03b2 signaling. Together, these findings demonstrate that quantitative and targeted modulation of defined adhesion cues enables programmable control of transcriptomic states in pancreatic cancer organoids.<\/jats:p>","DOI":"10.1002\/adma.202517390","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T07:42:12Z","timestamp":1776152532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bottom\u2010Up Programming of Cell States in Cancer Organoids with Defined Synthetic Adhesion Cues"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-1601","authenticated-orcid":false,"given":"Ali","family":"Nadernezhad","sequence":"first","affiliation":[{"name":"Division of Polymer Biomaterials Science Leibniz Institute of Polymer Research Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena 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