Cited by 7983D Printing in Biomedical ResearchCancer Cells and MetastasisAnimal testing and alternatives

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The use of 3-d cultures for high-throughput screening: the multicellular spheroid model.

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Kunz-Schughart, Leoni A., Freyer, James P., Hofstaedter, Ferdinand, Ebner, Reinhard·2004·SLAS DISCOVERY

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Abstract

Over the past few years, establishment and adaptation of cell-based assays for drug development and testing has become an important topic in high-throughput screening (HTS). Most new assays are designed to rapidly detect specific cellular effects reflecting action at various targets. However, although more complex than cell-free biochemical test systems, HTS assays using monolayer or suspension cultures still reflect a highly artificial cellular environment and may thus have limited predictive value for the clinical efficacy of a compound. Today's strategies for drug discovery and development, be they hypothesis free or mechanism based, require facile, HTS-amenable test systems that mimic the human tissue environment with increasing accuracy in order to optimize preclinical and preanimal selection of the most active molecules from a large pool of potential effectors, for example, against solid tumors. Indeed, it is recognized that 3-dimensional cell culture systems better reflect the in vivo behavior of most cell types. However, these 3-D test systems have not yet been incorporated into mainstream drug development operations. This article addresses the relevance and potential of 3-D in vitro systems for drug development, with a focus on screening for novel antitumor drugs. Examples of 3-D cell models used in cancer research are given, and the advantages and limitations of these systems of intermediate complexity are discussed in comparison with both 2-D culture and in vivo models. The most commonly used 3-D cell culture systems, multicellular spheroids, are emphasized due to their advantages and potential for rapid development as HTS systems. Thus, multicellular tumor spheroids are an ideal basis for the next step in creating HTS assays, which are predictive of in vivo antitumor efficacy.

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Authors: Kunz-Schughart, L. A., Freyer, J. P., Hofstaedter, F., & Ebner, R.
Affiliations: Los Alamos National Laboratory (US)
University of Regensburg (DE)
Avalon Pharma (United States) (US)
Venue: SLAS DISCOVERY
Publisher: Elsevier BV
Published: 2004-06
Volume: 9
Issue: 4
Pages: 273-285
ISSN: 2472-5552 (ISSN-L)
DOI: 10.1177/1087057104265040
OpenAlex: W2140723257
Cited by: 797
References: 163
Citations by year: 2026: 21 · 2025: 26 · 2024: 24 · 2023: 29 · 2022: 38 · 2021: 38 · 2020: 45 · 2019: 39 · 2018: 51 · 2017: 61 · 2016: 63 · 2015: 50 · 2014: 46 · 2013: 58 · 2012: 29
FWCI: 11.64
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 6538 d)
Locations: SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
Topics: Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Keywords: tumor spheroids, 3D cell culture, high-throughput screening, anticancer drug screening, drug development, solid tumors, cell-based assays
MeSH terms: Animals, Antineoplastic Agents, Drug Evaluation, Preclinical, Drug Screening Assays, Antitumor, Humans, Models, Biological, Tumor Cells, Cultured, Spheroids, Cellular, In Vitro Techniques

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The use of 3-d cultures for high-throughput screening: the multicellular spheroid model.

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