Gliamimic: A Longitudinal, Multimodal in Vitro Platform for Evaluating Glioblastoma Treatment Response and Post-treatment Tumor Progression in Patient-derived Organoids or Spheroids

Gliamimic: A Longitudinal, Multimodal in Vitro Platform for Evaluating Glioblastoma Treatment Response and Post-treatment Tumor Progression in Patient-derived Organoids or Spheroids | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Gliamimic: A Longitudinal, Multimodal in Vitro Platform for Evaluating Glioblastoma Treatment Response and Post-treatment Tumor Progression in Patient-derived Organoids or Spheroids Selina Camenisch, Luisa Bell, Nadine Stokar-Regenscheit, Natalia Vélez Char, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9496939/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Treatment resistance and recurrence continue to define the clinical landscape of glioblastoma (GBM), yet their study is limited by traditional in vitro frameworks that fail to capture long-term treatment dynamics and tumor evolution. Here we present GliaMimic, a longitudinal in vitro platform incorporating irradiation and multi-dose temozolomide (TMZ) in a down-scaled regimen inspired by the clinical Stupp protocol. Using patient-derived organoids (PDOs) and cell line-derived spheroids, tumor progression and treatment response were monitored non-invasively over four weeks. Substantial declines in metabolic activity and viability at clinically relevant TMZ concentrations (≤ 10 µM) emerge only after prolonged exposure, whereas short-term assays captured effects only at supraphysiological doses. Quantitative GliaScore and post-treatment performance metrics used for integrating and comparing longitudinal GliaMimic data, revealed a broad spectrum of treatment responses across MGMT- unmethylated PDOs, reflecting clinical heterogeneity in GBM. Notably, PDOs, patient-derived spheroids, and their cell line-derived counterparts exhibited distinct patterns of treatment response and tumor progression, underscoring the importance of model selection in preclinical studies. Following treatment cessation, the platform captured distinct, patient-specific post-treatment tumor behaviors with persistent viable and metabolically active populations across all models with more pronounced changes in PDOs. By moving beyond static molecular diagnostics, GliaMimic provides a platform for personalized treatment evaluation and preclinical testing. Glioblastoma patient-derived organoids preclinical models in vitro Stupp regime relapse assessment precision medicine Full Text Additional Declarations Competing interest reported. L.B and N.S.-R. were employees and shareholders of F. Hoffmann-La Roche Ltd at the time the work was completed. Supplementary Files GliaMimicSupplementaryMaterial.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 01 May, 2026 Reviewers invited by journal 24 Apr, 2026 Editor assigned by journal 24 Apr, 2026 Submission checks completed at journal 24 Apr, 2026 First submitted to journal 22 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9496939","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":634249287,"identity":"08cd3dc0-b935-4ac3-8764-39ad55523797","order_by":0,"name":"Selina Camenisch","email":"","orcid":"","institution":"Swiss Federal Laboratories for Materials Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Selina","middleName":"","lastName":"Camenisch","suffix":""},{"id":634249288,"identity":"0595c3a6-9709-48ca-8cfd-b87b1b67a2cb","order_by":1,"name":"Luisa Bell","email":"","orcid":"","institution":"Roche 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