Three-dimensional cell culture models in oncology: From tumour spheroids to integrated microphysiological systems
Abstract
Traditional two-dimensional (2D) cell cultures fail to capture the structural, mechanical, and biochemical complexity of living tissues, prompting a major paradigm shift toward three-dimensional (3D) cell culture models. 3D systems faithfully replicate in vivo physiological architectures, dynamic cell-to-cell contacts, and extracellular matrix (ECM) interactions, bridging a critical gap in preclinical studies by predicting human therapeutic responses more accurately. This review explores the technological evolution from simple multicellular tumor spheroids to sophisticated microphysiological networks. Scaffold-free methods-including the hanging drop, low-adherent plates, magnetic levitation, and dynamic bioreactors-efficiently recreate the pathophysiological oxygen, nutrient, and metabolic gradients characteristic of solid tumor zonation and drugresistance pathways. Conversely, scaffold-based systems leverage hydrogels, synthetic polymers, and decellularized matrices to dissect the biomechanics of matrix stiffness and mechanotransduction. At a higher tier of biological fidelity, patient-derived organoids preserve cellular heterogeneity, native tissue polarity, and accurate patient-specific mutational profiles, serving as critical pipelines for personalized medicine and precision drug screening. Furthermore, the integration of advanced microfluidic technologies has facilitated the engineering of tumor-, organ-, and multi-organ body-on-a-chip platforms. These microphysiological systems reconstruct dynamic fluid flow, functional tissue-vascular interfaces, physiological barriers (such as the blood-brain barrier), and systemic pharmacokinetic/pharmacodynamic (ADME) drug profiles. Beyond deepening mechanistic insights into oncology, these interconnected 3D models provide highly ethical, predictive, and cost-effective alternatives to animal experimentation in strict alignment with the 3Rs principles. Ultimately, these complementary 3D culture technologies are transforming oncology into a highly predictive, patient-tailored discipline
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BibTeX
@article{martin2026threedimensional,
title = {{Three-dimensional cell culture models in oncology: From tumour spheroids to integrated microphysiological systems}},
author = {Eva Martin and Flavien Bessaguet and Nicolas Clere},
journal = {Pharmacological Research},
year = {2026},
month = oct,
doi = {10.1016/j.phrs.2026.108465},
url = {https://hal.science/hal-05777912v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Three-dimensional cell culture models in oncology: From tumour spheroids to integrated microphysiological systems
AU - Eva Martin
AU - Flavien Bessaguet
AU - Nicolas Clere
PY - 2026
DA - 2026/10/05
JO - Pharmacological Research
DO - 10.1016/j.phrs.2026.108465
UR - https://hal.science/hal-05777912v1
AB - Traditional two-dimensional (2D) cell cultures fail to capture the structural, mechanical, and biochemical complexity of living tissues, prompting a major paradigm shift toward three-dimensional (3D) cell culture models. 3D systems faithfully replicate in vivo physiological architectures, dynamic cell-to-cell contacts, and extracellular matrix (ECM) interactions, bridging a critical gap in preclinical studies by predicting human therapeutic responses more accurately. This review explores the technological evolution from simple multicellular tumor spheroids to sophisticated microphysiological networks. Scaffold-free methods-including the hanging drop, low-adherent plates, magnetic levitation, and dynamic bioreactors-efficiently recreate the pathophysiological oxygen, nutrient, and metabolic gradients characteristic of solid tumor zonation and drugresistance pathways. Conversely, scaffold-based systems leverage hydrogels, synthetic polymers, and decellularized matrices to dissect the biomechanics of matrix stiffness and mechanotransduction. At a higher tier of biological fidelity, patient-derived organoids preserve cellular heterogeneity, native tissue polarity, and accurate patient-specific mutational profiles, serving as critical pipelines for personalized medicine and precision drug screening. Furthermore, the integration of advanced microfluidic technologies has facilitated the engineering of tumor-, organ-, and multi-organ body-on-a-chip platforms. These microphysiological systems reconstruct dynamic fluid flow, functional tissue-vascular interfaces, physiological barriers (such as the blood-brain barrier), and systemic pharmacokinetic/pharmacodynamic (ADME) drug profiles. Beyond deepening mechanistic insights into oncology, these interconnected 3D models provide highly ethical, predictive, and cost-effective alternatives to animal experimentation in strict alignment with the 3Rs principles. Ultimately, these complementary 3D culture technologies are transforming oncology into a highly predictive, patient-tailored discipline
SN - 1043-6618
SN - 1096-1186
ER -