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A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy

David Ascheid, Magdalena Baumann, Jürgen Pinnecker, Mike Friedrich, Daniel Szi-Marton, Cornelia Medved, Maja Bundalo, Vanessa Ortmann, Asli Öztürk, Rajender Nandigama, Katherina Hemmen, Süleymann Ergün, Alma Zernecke, Matthias Hirth, Katrin G. Heinze () and Erik Henke ()
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David Ascheid: Julius-Maximilians-Universität Würzburg
Magdalena Baumann: Julius-Maximilians-Universität Würzburg
Jürgen Pinnecker: Julius-Maximilians-Universität Würzburg
Mike Friedrich: Julius-Maximilians-Universität Würzburg
Daniel Szi-Marton: Julius-Maximilians-Universität Würzburg
Cornelia Medved: Julius-Maximilians-Universität Würzburg
Maja Bundalo: Universitätsklinikum Würzburg
Vanessa Ortmann: Julius-Maximilians-Universität Würzburg
Asli Öztürk: Julius-Maximilians-Universität Würzburg
Rajender Nandigama: Julius-Maximilians-Universität Würzburg
Katherina Hemmen: Julius-Maximilians-Universität Würzburg
Süleymann Ergün: Julius-Maximilians-Universität Würzburg
Alma Zernecke: Universitätsklinikum Würzburg
Matthias Hirth: Technische Universität Illmenau
Katrin G. Heinze: Julius-Maximilians-Universität Würzburg
Erik Henke: Julius-Maximilians-Universität Würzburg

Nature Communications, 2024, vol. 15, issue 1, 1-23

Abstract: Abstract Targeting the supportive tumor microenvironment (TME) is an approach of high interest in cancer drug development. However, assessing TME-targeted drug candidates presents a unique set of challenges. We develop a comprehensive screening platform that allows monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumor spheroids (VTSs). The confrontation of four human-derived cell populations makes it possible to recreate and study complex changes in TME composition and cell-cell interaction. The platform is modular and adaptable for tumor entity or genetic manipulation. Treatment effects are recorded by light sheet fluorescence microscopy and translated by an advanced image analysis routine in processable multi-parametric datasets. The system proved to be robust, with strong interassay reliability. We demonstrate the platform’s utility for evaluating TME-targeted antifibrotic and antiangiogenic drugs side-by-side. The platform’s output enabled the differential evaluation of even closely related drug candidates according to projected therapeutic needs.

Date: 2024
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DOI: 10.1038/s41467-024-48010-z

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