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A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy
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A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy
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Journal Article
A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy
2024
Overview
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.
Assessing tumour microenvironment-targeted drug candidates remains challenging. Here, the authors develop a comprehensive screening platform that allows for monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumour spheroids.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/107
/ 13/31
/ 13/51
/ 14
/ 14/5
/ 14/63
/ 59
/ 82/29
/ Angiogenesis Inhibitors - pharmacology
/ Angiogenesis Inhibitors - therapeutic use
/ Antineoplastic Agents - pharmacology
/ Antineoplastic Agents - therapeutic use
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - pathology
/ Drug Screening Assays, Antitumor - methods
/ Female
/ Humanities and Social Sciences
/ Humans
/ Microscopy, Fluorescence - methods
/ Neovascularization, Pathologic - drug therapy
/ Neovascularization, Pathologic - pathology
/ Ranking
/ Science
/ Spheroids, Cellular - drug effects
/ Spheroids, Cellular - pathology
/ Tumor Microenvironment - drug effects
/ Tumors
