Mini organs for cancer drug discovery
Changing the way we find new cancer treatments by bringing organoid techniques to drug development scale.
Testing new potential cancer treatments on cells grown directly on petri dishes has many limitations. Cells laying on a flat surface are restricted in how accurately they can reflect the biology of a three-dimensional human organ in the body. Researchers needed an improved model for tumours, as well as a model that could be produced in the large quantities necessary for drug development. Scientists at Cardiff University were able to satisfy meet this unmet need.
What is an organoid?
Organoids are three-dimensional tissue structures that behave and act like miniature organs in a petri dish. They can be grown from patient biopsies from different organs in the body. Organoids from tumour tissue will contain cancer cells. Organoids better represent the complexity of human tissues and can allow researchers to test potential new cancer treatments more effectively and accurately.
Tumour organoids offer a powerful pre-clinical discovery tool for new anti-cancer drug treatments. But for organoids to be used in drug development, they needed to be produced in large quantities. They must also be uniform in size and structure and the batches must be reproducible.
“We developed a novel method for the growth of large quantities of uniform organoids, which – through a collaboration with the University of Bath, we were able to patent. This led to the establishment of a spin-out biotechnology company called Cellesce Ltd in 2015.” Professor Trevor Dale, School of Biosciences at Cardiff University.
Cellesce Ltd is currently valued at £15 million and has secured key contracts with global pharmaceutical and research development companies.
How it started
The team of Cardiff University researchers originally began working with organoids to study a pathway in which cells communicate with one another called the WNT signalling pathway. This mechanism plays a pivotal role in the development of colon cancer.
More than 90% of human colon cancers have genetic mutations that cause a disruption in the function of the WNT signalling pathway. WNT signalling is also crucial to the formation of intestinal organoids.
In 2012, the researchers used cells from small pieces of colon tumour collected from consented patients to develop organoids that mimic the intestines. They were able to use these intestinal organoids to test new potential therapies that target the WNT signalling pathway.
The unique process developed by Cellesce Ltd allows increased production of organoids in both scale and uniformity, compared to other methods. This enables more accuracy and repeatability when testing new cancer drugs. Each batch consists of up to 5 million organoids, sufficient for around 30,000 drug tests per batch. Other methods of organoid formation support around 1,000 drug tests per batch.
By applying their research expertise in cancer organoid models to develop a patented process, the researchers at Cardiff University and Cellesce Ltd were able to provide high quality organoid cultures for pharmaceutical companies across the globe, for use in drug discovery.
Meet the team
Key contacts
Publications
- Badder, L. M. et al. 2020. 3D imaging of colorectal cancer organoids identifies responses to Tankyrase inhibitors. PLoS ONE 15 (8) e0235319. (10.1371/journal.pone.0235319)
- Hollins, A. J. and Parry, L. 2016. Long-term culture of intestinal cell progenitors: an overview of their development, application, and associated technologies. Current Pathobiology Reports 4 (4), pp.209-219. (10.1007/s40139-016-0119-1)
- Jardé, T. et al., 2016. Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids. Nature Communications 7 13207. (10.1038/ncomms13207)
- Dale, T. et al. 2015. A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nature Chemical Biology 11 , pp.973-980. (10.1038/nchembio.1952)
- Jarde, T. et al. 2013. In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-OΔN89β-catenin system. Oncogene 32 (7), pp.883-893. (10.1038/onc.2012.103)
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