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3D bioprinted cancer models: from basic biology to drug development

Nature Reviews Cancer volume 22, pages 679–692 (2022)Cite this article

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Abstract

Effort invested in the development of new drugs often fails to be translated into meaningful clinical benefits for patients with cancer. The development of more effective anticancer therapeutics and accurate prediction of their clinical merit remain urgent unmet medical needs. As solid cancers have complex and heterogeneous structures composed of different cell types and extracellular matrices, three-dimensional (3D) cancer models hold great potential for advancing our understanding of cancer biology, which has been historically investigated in tumour cell cultures on rigid plastic plates. Advanced 3D bioprinted cancer models have the potential to revolutionize the way we discover therapeutic targets, develop new drugs and personalize anticancer therapies in an accurate, reproducible, clinically translatable and robust manner. These ex vivo cancer models are already replacing existing in vitro systems and could, in the future, diminish or even replace the use of animal models. Therefore, profound understanding of the differences in tumorigenesis between 2D, 3D and animal models of cancer is essential. This Review presents the state of the art of 3D bioprinted cancer modelling, focusing on the biological processes that underlie the molecular mechanisms involved in cancer progression and treatment response as well as on proteomic and genomic signatures.

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Fig. 1: A timeline showing the development of 3D bioprinted cancer models.
Fig. 2: 3D bioprinted models of cancer cell growth, migration, invasion, stemness and gene expression.
Fig. 3: Use of 3D bioprinted models to investigate drug efficacy.

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Acknowledgements

The authors acknowledge partial funding from the European Research Council (ERC) Advanced Grant Agreement no. 835227-3DBrainStorm; ERC Proof of Concept Grant (862580; 3DCanPredict) and the Morris Kahn Foundation (all to R.S.F.). L.N. and E.Y. acknowledge the financial support of their fellowship from the Dan David Prize.

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  1. These authors contributed equally: Lena Neufeld, Eilam Yeini, Sabina Pozzi.

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Lena Neufeld, Eilam Yeini, Sabina Pozzi & Ronit Satchi-Fainaro

  2. Sagol School of Neurosciences, Tel Aviv University, Tel Aviv, Israel

    Ronit Satchi-Fainaro

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Correspondence to Ronit Satchi-Fainaro.

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R.S.F. declares that she is a Director on the board of Teva Pharmaceutical Industries and receives research funding from Merck for work unrelated to this manuscript. All other authors declare no competing interests.

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Glossary

Shear thinning

A reduction in viscosity caused by shear stress — the physical forces created by liquid flow parallel to the surface of a material.

Perfusable channels

Directional fluid flow can be applied via artificial vessels, in which it is possible to control the speed, rate and composition of the circulating fluid.

Bioink

A composition of materials that can be deposited by a 3D bioprinter to produce a tissue that supports living cells in a 3D manner.

Crosslinking

Formation of permanent or reversible bonds between neighbouring polymer chains creating a network structure.

Decellularized

Natural scaffolds derived from tissues or organs, in which the cellular and nuclear contents are eliminated but the 3D structure and composition of the extracellular matrix are preserved.

Sacrificial bioink

Bioink materials that can be printed and embedded into other materials while forming a solid gel structure and can later be dissolved to create hollow parts, such as microfluidic channels or vascular networks.

Rheology

The science of deformation of materials.

Epithelial-to-mesenchymal transition

(EMT). A process of phenotypic and transcriptomic change in which epithelial-like cells acquire mesenchymal-like properties, such as the ability to detach from their neighbours and migrate to distant sites.

Support bath

A platform that supports low viscosity bioinks extruded within its volume, until they are crosslinked into complex structures.

Isotropic

Mechanical and physical properties that are not affected by the orientation of the atoms when organized in their crystal structure. Isotropic behaviour is observed in pathological remodelling of the extracellular matrix, which facilitates tumour cell invasion.

Anisotropic

Mechanical and physical properties that are affected by the orientation of the atoms when organized in their crystal structure.

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Neufeld, L., Yeini, E., Pozzi, S. et al. 3D bioprinted cancer models: from basic biology to drug development. Nat Rev Cancer 22, 679–692 (2022). https://doi.org/10.1038/s41568-022-00514-w

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