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Next generation organoid engineering to replace animals in cancer drug testing

Lookup NU author(s): Sean Hockney, Jasmin TurnerORCiD, Dr Stephen Todryk, Dr Gerrit HilgenORCiD, Dr Deepali Pal



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 The AuthorsCancer therapies have several clinical challenges associated with them, namely treatment toxicity, treatment resistance and relapse. Due to factors ranging from patient profiles to the tumour microenvironment (TME), there are several hurdles to overcome in developing effective treatments that have low toxicity that can mitigate emergence of resistance and occurrence of relapse. De novo cancer development has the highest drug attrition rates with only 1 in 10,000 preclinical candidates reaching the market. To alleviate this high attrition rate, more mimetic and sustainable preclinical models that can capture the disease biology as in the patient, are required. Organoids and next generation 3D tissue engineering is an emerging area that aims to address this problem. Advancement of three-dimensional (3D) in vitro cultures into complex organoid models incorporating multiple cell types alongside acellular aspects of tissue microenvironments can provide a system for therapeutic testing. Development of microfluidic technologies have furthermore increased the biomimetic nature of these models. Additionally, 3D bio-printing facilitates generation of tractable ex vivo models in a controlled, scalable and reproducible manner. In this review we highlight some of the traditional preclinical models used in cancer drug testing and debate how next generation organoids are being used to replace not only animal models, but also some of the more elementary in vitro approaches, such as cell lines. Examples of applications of the various models will be appraised alongside the future challenges that still need to be overcome.

Publication metadata

Author(s): Hockney S, Parker J, Turner JE, Todd X, Todryk S, Gieling RG, Hilgen G, Simoes DCM, Pal D

Publication type: Review

Publication status: Published

Journal: Biochemical Pharmacology

Year: 2023

Volume: 213

Print publication date: 01/07/2023

Online publication date: 08/05/2023

Acceptance date: 28/04/2023

ISSN (print): 0006-2952

ISSN (electronic): 1873-2968

Publisher: Elsevier Inc.


DOI: 10.1016/j.bcp.2023.115586

PubMed id: 37164297