3D cell culture systems modeling tumor growth determinants in cancer target discovery
Abstract
Phenotypic heterogeneity of cancer cells, cell biological context, heterotypic crosstalk and the microenvironment are key determinants of the multistep process of tumor development. They sign responsible, to a significant extent, for the limited response and resistance of cancer cells to molecular-targeted therapies. Better functional knowledge of the complex intra- and intercellular signaling circuits underlying communication between the different cell types populating a tumor tissue and of the systemic and local factors that shape the tumor microenvironment is therefore imperative. Sophisticated 3D multicellular tumor spheroid (MCTS) systems provide an emerging tool to model the phenotypic and cellular heterogeneity as well as microenvironmental aspects of in vivo tumor growth. In this review we discuss the cellular, chemical and physical factors contributing to zonation and cellular crosstalk within tumor masses. On this basis, we further describe 3D cell culture technologies for growth of MCTS as advanced tools for exploring molecular tumor growth determinants and facilitating drug discovery efforts. We conclude with a synopsis on technological aspects for on-line analysis and post-processing of 3D MCTS models.
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Tissue-engineered 3D tumor models consisting of spheroids or organoids grown within synthetic ECM constructs have enabled more rigorous tissue-level studies of the TIME and restore important architectural and stromal cues.
“Tissue-engineered 3D tumor models [100, 101], consisting of spheroids or organoids grown within synthetic ECM constructs, have enabled more rigorous tissue level studies of the TIME, and restore important architectural and stromal cues [102]”
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- Authors
- Thoma, C. R., Zimmermann, M., Agarkova, I., Kelm, J. M., & Krek, W.
- Affiliations
- ETH Zurich (CH)
- Corresponding author
- Thoma, Claudio R.
- Krek, Wilhelm
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 69-70
- Pages
- 29-41
- ISSN
- 0169-409X (ISSN-L)
- OpenAlex
- W1976767579
- Cited by
- 478
- References
- 155
- Citations by year
- 2026: 9 · 2025: 24 · 2024: 32 · 2023: 31 · 2022: 29 · 2021: 48 · 2020: 60 · 2019: 51 · 2018: 56 · 2017: 46 · 2016: 48 · 2015: 35 · 2014: 9
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- tumor spheroids, 3D cell culture, tumor microenvironment, tumor heterogeneity, cell-cell crosstalk, anticancer drug discovery, drug resistance, targeted therapy
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Neoplasms, Spheroids, Cellular, Cell Culture Techniques, Drug Discovery, Tumor Microenvironment
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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