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The Humane Research Trust is funding a research project to provide an optimal human-based model for testing bowel cancer treatments. Researchers at the University of Nottingham developed a new technique to replicate the tumour environment in the lab. This research will help us identify effective treatments and provide a framework for application in other cancer research areas.
Bowel cancer is an aggressive cancer that kills over 16,500 people in the UK every year. At present, we do not have effective bowel cancer drugs. Researchers are concerned that current drug testing and prediction models and technologies are inadequate. The tumour environment is complex, with research suggesting that the substances secreted around the tumour may have a role.
“Animal studies have been limited in that they do not precisely model human tumours,” explains Dr Abdolrahman Shams Nateri, Associate Professor in Cancer Genetics and Stem Cells at the University of Nottingham. “As a result, newly developed bowel cancer drugs regularly fail clinical testing. This delays progress and leads to a positive feedback loop of greater animal experimentation to validate the next best targets.”
A popular animal-free technique within cancer research makes use of lab-made ‘organoids’. Researchers can partially recreate the complexity of human bowel tissues in a dish. They grow these organoids, also called 'mini-gut organs;, as three-dimensional structures, and use them to test potential cancer treatments. However, Dr Nateri warns that since these organoids lack immune cells, they are not able to reproduce the cell interactions found in tumours.
In real cancer cases, the substances secreted around tumours mediate the cell interactions. We call this outer environment of secretions the 'tumour matrix'. One such secretion within the tumour matrix is a molecule known as ‘SPOCK1 protein’. The data suggests that SPOCK1 may play an essential role in the tumour matrix of various cancer types. As SPOCK1 secretes into and circulates via the blood, it may impact patients’ responses to drugs.
The Humane Research Trust is currently funding Dr Nateri to lead a new bowel cancer research. Within this project, the research group are recreating a more accurate bowel tumour environment in the lab. Dr Nateri and his research group are using a model called a ‘patient-derived explant’ (PDE) within their study. This model is advantageous in that it retains the complexity of the tumour environment.
The researchers combine the patient-derived explant with a ‘mini-ring system.’ Essentially, scientists mix a ring of tumour explant material with tumour matrix around the wall of the microplate. This means they can test potential treatments and quickly ascertain drug sensitivity and clinical benefit. The SPOCK1 secretion is an unfavourable biomarker in the tumour matrix. Thus, scientists can use this model to develop treatments which effectively target it.
In addition, Dr Nateri believes that scientists can apply this model to other organs, including lung, pancreas, and breast cancers. Dr Nateri said: “We encourage other research groups to consider using patient-derived mini-ring technology systems. This will lead to significant replacement and, subsequently, reduction of animals in research.”
