Multicellular tumor spheroids: An underestimated tool is catching up again
Abstract
The present article highlights the rationale, potential and flexibility of tumor spheroid mono- and cocultures for implementation into state of the art anti-cancer therapy test platforms. Unlike classical monolayer-based models, spheroids strikingly mirror the 3D cellular context and therapeutically relevant pathophysiological gradients of in vivo tumors. Some concepts for standardization and automation of spheroid culturing, monitoring and analysis are discussed, and the challenges to define the most convenient analytical endpoints for therapy testing are outlined. The potential of spheroids to contribute to either the elimination of poor drug candidates at the pre-animal and pre-clinical state or the identification of promising drugs that would fail in classical 2D cell assays is emphasised. Microtechnologies, in the form of micropatterning and microfluidics, are also discussed and offer the exciting prospect of standardized spheroid mass production to tackle high-throughput screening applications within the context of traditional laboratory settings. The extension towards more sophisticated spheroid coculture models which more closely reflect heterologous tumor tissues composed of tumor and various stromal cell types is also covered. Examples are given with particular emphasis on tumor-immune cell cocultures and their usefulness for testing novel immunotherapeutic treatment strategies. Finally, tumor cell heterogeneity and the extraordinary possibilities of putative cancer…
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Three-dimensional multicellular tumor spheroids capture essential features of tumor architecture, stromal interactions, and microenvironmental resistance mechanisms.
“Three-dimensional multicellular tumor spheroids have emerged as more representative in vitro models that capture essential features of tumor architecture, stromal interactions, and microenvironmental resistance mechanisms.”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [16]
Multicellular tumor spheroids provide a more physiologically relevant context for evaluating anticancer agents and delivery systems by mimicking the hierarchical structure, proliferation gradients, and stromal interactions found in native tumor tissues.
“By mimicking the hierarchical structure, proliferation gradients, and stromal interactions found in native tumor tissues, spheroids provide a more physiologically relevant context for evaluating anticancer agents and delivery systems [16,17].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [16]
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- Authors
- Hirschhaeuser, F., Menne, H., Dittfeld, C., West, J., Mueller-Klieser, W., & Kunz-Schughart, L. A.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Leibniz Institute for Analytical Sciences - ISAS (DE)
- OncoRay (DE)
- Venue
- Journal of Biotechnology
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 148
- Issue
- 1
- Pages
- 3-15
- ISSN
- 0168-1656 (ISSN-L)
- OpenAlex
- W2136445803
- Cited by
- 1,674
- References
- 5
- Citations by year
- 2026: 71 · 2025: 90 · 2024: 99 · 2023: 96 · 2022: 92 · 2021: 122 · 2020: 129 · 2019: 128 · 2018: 132 · 2017: 138 · 2016: 157 · 2015: 104 · 2014: 119 · 2013: 95 · 2012: 48
- FWCI
- 31.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- tumor spheroids, anticancer drug screening, 3D tumor models, therapeutic endpoints, micropatterning, microfluidics, high-throughput screening, tumor stroma, tumor heterogeneity, cancer stem cells, drug development
- MeSH terms
- Animals, Drug Evaluation, Preclinical, Humans, Tumor Cells, Cultured, Spheroids, Cellular, Coculture Techniques, Microfluidic Analytical Techniques, Mice, High-Throughput Screening Assays
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