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Review

Two-Dimensional and Spheroid-Based Three-Dimensional Cell Culture Systems: Implications for Drug Discovery in Cancer

by
Anali del Milagro Bernabe Garnique
1,
Natália Sudan Parducci
1,
Lívia Bassani Lins de Miranda
1,
Bruna Oliveira de Almeida
1,
Leonardo Sanches
2 and
João Agostinho Machado-Neto
1,*
1
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo CEP 05508-900, Brazil
2
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo CEP 05508-900, Brazil
*
Author to whom correspondence should be addressed.
Drugs Drug Candidates 2024, 3(2), 391-409; https://doi.org/10.3390/ddc3020024
Submission received: 16 April 2024 / Revised: 6 June 2024 / Accepted: 11 June 2024 / Published: 13 June 2024
(This article belongs to the Section Preclinical Research)
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Abstract

The monolayer (two-dimensional or 2D) cell culture, while widely used, lacks fidelity in replicating vital cell interactions seen in vivo, leading to a shift toward three-dimensional (3D) models. Although monolayers offer simplicity and cost-effectiveness, spheroids mimic cellular environments better. This is due to its nutrient gradients, which influence drug penetration and provide a more accurate reflection of clinical scenarios than monolayers. Consequently, 3D models are crucial in drug development, especially for anti-cancer therapeutics, enabling the screening of cell cycle inhibitors and combination therapies vital for heterogeneous tumor populations. Inhibiting processes like migration and invasion often require drugs targeting the cytoskeleton, which can exhibit dual functionality with cell cycle inhibitors. Therapeutic approaches with promising anti-cancer potential often exhibit reduced efficacy in 3D cell culture compared to their performance in monolayer settings, primarily due to the heightened complexity inherent in this system. In the face of this scenario, this review aims to survey existing knowledge on compounds utilized in both 2D and 3D cell cultures, assessing their responses across different culture types and discerning the implications for drug screening, particularly those impacting the cell cycle and cytoskeletal dynamics.
Keywords: cell cycle drugs; cytoskeleton drugs; monolayer; spheroids; 3D cell culture cell cycle drugs; cytoskeleton drugs; monolayer; spheroids; 3D cell culture
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MDPI and ACS Style

Garnique, A.d.M.B.; Parducci, N.S.; de Miranda, L.B.L.; de Almeida, B.O.; Sanches, L.; Machado-Neto, J.A. Two-Dimensional and Spheroid-Based Three-Dimensional Cell Culture Systems: Implications for Drug Discovery in Cancer. Drugs Drug Candidates 2024, 3, 391-409. https://doi.org/10.3390/ddc3020024

AMA Style

Garnique AdMB, Parducci NS, de Miranda LBL, de Almeida BO, Sanches L, Machado-Neto JA. Two-Dimensional and Spheroid-Based Three-Dimensional Cell Culture Systems: Implications for Drug Discovery in Cancer. Drugs and Drug Candidates. 2024; 3(2):391-409. https://doi.org/10.3390/ddc3020024

Chicago/Turabian Style

Garnique, Anali del Milagro Bernabe, Natália Sudan Parducci, Lívia Bassani Lins de Miranda, Bruna Oliveira de Almeida, Leonardo Sanches, and João Agostinho Machado-Neto. 2024. "Two-Dimensional and Spheroid-Based Three-Dimensional Cell Culture Systems: Implications for Drug Discovery in Cancer" Drugs and Drug Candidates 3, no. 2: 391-409. https://doi.org/10.3390/ddc3020024

APA Style

Garnique, A. d. M. B., Parducci, N. S., de Miranda, L. B. L., de Almeida, B. O., Sanches, L., & Machado-Neto, J. A. (2024). Two-Dimensional and Spheroid-Based Three-Dimensional Cell Culture Systems: Implications for Drug Discovery in Cancer. Drugs and Drug Candidates, 3(2), 391-409. https://doi.org/10.3390/ddc3020024

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