Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Dec 31;14(1):190.
doi: 10.3390/cancers14010190.

3D Cell Culture Models as Recapitulators of the Tumor Microenvironment for the Screening of Anti-Cancer Drugs

Mélanie A G Barbosa  1   2 , Cristina P R Xavier  1   2 , Rúben F Pereira  2   3   4 , Vilma Petrikaitė  5   6 , M Helena Vasconcelos  1   2   7
Affiliations
Review

3D Cell Culture Models as Recapitulators of the Tumor Microenvironment for the Screening of Anti-Cancer Drugs

Mélanie A G Barbosa et al. Cancers (Basel). .

Abstract

Today, innovative three-dimensional (3D) cell culture models have been proposed as viable and biomimetic alternatives for initial drug screening, allowing the improvement of the efficiency of drug development. These models are gaining popularity, given their ability to reproduce key aspects of the tumor microenvironment, concerning the 3D tumor architecture as well as the interactions of tumor cells with the extracellular matrix and surrounding non-tumor cells. The development of accurate 3D models may become beneficial to decrease the use of laboratory animals in scientific research, in accordance with the European Union's regulation on the 3R rule (Replacement, Reduction, Refinement). This review focuses on the impact of 3D cell culture models on cancer research, discussing their advantages, limitations, and compatibility with high-throughput screenings and automated systems. An insight is also given on the adequacy of the available readouts for the interpretation of the data obtained from the 3D cell culture models. Importantly, we also emphasize the need for the incorporation of additional and complementary microenvironment elements on the design of 3D cell culture models, towards improved predictive value of drug efficacy.

Keywords: 3D cell culture models; cellular co-culture; preclinical assays; stromal cells; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The main features and advantages/disadvantages of 3D cell models in comparison to 2D cell models (cells grown in monolayers).
Figure 2
Figure 2
Schematic representation of the different 3D cell culture techniques.
See this image and copyright information in PMC

References

    1. Singh S., Sharma B., Kanwar S.S., Kumar A. Lead Phytochemicals for Anticancer Drug Development. Front. Plant Sci. 2016;7 doi: 10.3389/fpls.2016.01667. - DOI - PMC - PubMed
    1. Scannell J.W., Bosley J. When Quality Beats Quantity: Decision Theory, Drug Discovery, and the Reproducibility Crisis. PLoS ONE. 2016;11:e0147215. doi: 10.1371/journal.pone.0147215. - DOI - PMC - PubMed
    1. Sharma M.R., Stadler W.M., Ratain M.J. Randomized phase II trials: A long-term investment with promising returns. J. Natl. Cancer Inst. 2011;103:1093–1100. doi: 10.1093/jnci/djr218. - DOI - PMC - PubMed
    1. Jardim D.L., Groves E.S., Breitfeld P.P., Kurzrock R. Factors associated with failure of oncology drugs in late-stage clinical development: A systematic review. Cancer Treat. Rev. 2017;52:12–21. doi: 10.1016/j.ctrv.2016.10.009. - DOI - PubMed
    1. Lin A., Giuliano C.J., Palladino A., John K.M., Abramowicz C., Yuan M.L., Sausville E.L., Lukow D.A., Liu L., Chait A.R., et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl. Med. 2019;11 doi: 10.1126/scitranslmed.aaw8412. - DOI - PMC - PubMed

LinkOut - more resources