The DOI matches its Crossref record; 271 of the 271 references it cites were found in a registry or an index.
Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research
Open accessAbstract
Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell–cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.
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“Despite their widespread use, conventional two-dimensional monolayer cultures fail to reproduce these complexities, contributing to the poor translational predictability of many preclinical candidates.”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [6]
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“While these models are convenient and scalable, they fail to capture essential characteristics such as spatial cell–cell interactions, oxygen and nutrient gradients, and ECM-mediated diffusion resistance—factors that critically influence drug behavior in solid tumors [6,7].”
Metadata
- Authors
- Pinto, B., Henriques, A. C., Silva, P. M. A., & Bousbaa, H.
- Affiliations
- Cooperativa de Ensino Superior Politécnico e Universitário (PT)
- Universidade do Porto (PT)
- Corresponding author
- Bousbaa, Hassan
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2020-12-06
- Volume
- 12
- Issue
- 12
- Pages
- 1186
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC7762220
- OpenAlex
- W3111112091
- Cited by
- 440
- References
- 271
- Citations by year
- 2026: 64 · 2025: 97 · 2024: 103 · 2023: 89 · 2022: 56 · 2021: 31
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Cooperativa de Ensino Superior Politécnico e Universitário (IMPLDEBRIS-PL-3RL-IINFACTS-2019, BD/CBAS/CESPU/01/2020)
- Fundação para a Ciência e a Tecnologia (SFRH/BD/116167/2016)
- 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
- multicellular spheroids, 3D tumor models, tumor cell culture, tumor microenvironment, preclinical drug screening, targeted therapy
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