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Updated: Jul 31, 2025
Generation of Tumor Organoids from Genetically Engineered Mouse Models of Prostate Cancer
Published on: June 13, 2019
Next generation organoid engineering to replace animals in cancer drug testing
Sean Hockney1, Jessica Parker1, Jasmin E Turner2
1Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.
Abstract:
Cancer 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.
Insights
Next-generation organoids and 3D tissue engineering offer advanced preclinical cancer models. These biomimetic systems improve drug testing, overcoming limitations of traditional methods and reducing high drug attrition rates.
Area of Science:
- Oncology
- Biomedical Engineering
- Drug Development
Background:
- Cancer therapies face challenges like toxicity, resistance, and relapse.
- Current preclinical models have high drug attrition rates (1 in 10,000 candidates reach market).
- Need for more biomimetic and sustainable preclinical models to accurately reflect patient disease biology.
Purpose of the Study:
- To review traditional preclinical cancer models.
- To discuss the role of next-generation organoids and 3D tissue engineering in cancer drug testing.
- To highlight advancements and future challenges in ex vivo cancer modeling.
Main Methods:
- Review of existing literature on preclinical cancer models.
- Discussion of organoid development and 3D tissue engineering.
- Integration of microfluidics and 3D bio-printing for enhanced model biomimicry.
- Appraisal of organoid applications compared to traditional models (cell lines, animal models).
Main Results:
- Organoids and advanced 3D models offer improved biomimicry and disease relevance.
- These next-generation models show potential to replace animal models and cell lines.
- Microfluidics and 3D bio-printing enhance model scalability, control, and reproducibility.
Conclusions:
- Next-generation organoids and 3D engineered tissues are crucial for overcoming preclinical model limitations.
- These advanced models promise to reduce drug attrition rates and improve therapeutic development.
- Further research is needed to address challenges in implementing these sophisticated ex vivo systems.
