Modelling tumours with experts in India to understand crucial cancer cell transitions

Dr Maria Secrier (UCL Faculty of Life Sciences) used UCL-IISc Strategic Partner Funds to collaborate with the Indian Institute of Science (IISc), to improve the modelling of cancer cells.

7 June 2024

The epithelial-to-mesenchymal transition in a cancerous tumour is a process when the state of some cells change. When these cells change into the mesenchymal state, they can detach from the primary tumour, enter the bloodstream, and migrate to other organs and form metastasis, which are secondary cancerous growths. This leads to poorer outcomes in patients. Modelling the make-up of tumours in more detail is crucial to understanding this cellular behaviour, so that treatments can eventually be developed to target this.

Dr Maria Secrier has a research interest in the epithelial-to-mesenchymal transition, and uses computational tools such as machine learning and big data analytics to understand this further. She was contacted by Dr Mohit Kumar Jolly from IISc, who has expertise in mathematical modelling, and shares a research interest in the epithelial-to-mesenchymal process. Believing that collaborating could pool knowledge and push forward understanding in this field, they were successful in their application for UCL-IISc Strategic Partner Funds.

Bringing together knowledge about cancer cell plasticity

As a result of the funding, Maria and Mohit have been able to visit each other鈥檚 labs multiple times, along with PhD students and other members of their teams. This enabled them to discuss their areas of interest and knowledge, so they could develop joint research ideas. Together, they organised a symposium at 皇家华人 about cancer cell plasticity and systems approaches to tackling cancer cell plasticity.聽

鈥淭his was a great opportunity to look into a topic that is currently emerging and quite unexplored in the context of cancer,鈥� Maria said. 鈥淭here's a lot of excitement in the field about it. We brought together a really diverse community of scientists working in cancer, as well as computational and data analytics. It helped us understand the opportunities and gaps in the field of cancer cell plasticity, as well as the epithelial-to-mesenchymal transition more specifically, which is one process within the bigger framework.鈥�

The symposium sparked a number of new collaborations, and feedback from attendees was very positive, with a lot of interest in making the symposium an annual event. The team is currently writing a review about the outcomes of the meeting. They also identified a need to use different computational approaches in their research on the epithelial-to-mesenchymal transition.

鈥淪patial transcriptomics is the main technique we鈥檙e working on together,鈥� Maria explained. 鈥淭his allows us to profile the entire cancer tissue. We can get a minute resolution of what鈥檚 going on within every single area of the tissue, understand what kinds of cells there are, how they interact with each other, and what molecular programmes are activated and deactivated. This is very important if we want to identify areas within the tumour that are more likely to resist treatment or lead to metastatic spread.鈥�

Previously, it has only been possible to take a cancer tissue sample and profile all the cells together. This means there is no information about individual cells, just a general understanding of the tumour as a whole. 鈥淭hat masks a lot of the heterogeneity within the tumour,鈥� Maria said. 鈥淭umours are really diverse. You have cells that have a different genetic makeup or subpopulations of cells. These can activate different molecular programmes in different parts of the tumour. It means that you might be able to successfully target and kill one part of the tumour with a drug, but maybe another part of tumour is resistant to the drug, meaning some cells survive.鈥澛�

Getting a more detailed understanding of the different cells within the tumour will help doctors tailor treatments better. The intracellular modelling the team is working on will enable them to make predictions based on the behaviour of different cells. They are also trying to identify different biomarkers to help understand the therapeutic response. Ultimately, it will pave the way for the development of more therapies that can target those cancer cells that are most likely to initiate metastases.

Becoming experts in the field

鈥淭his work has enabled us to start positioning ourselves as experts in this field,鈥� Maria said. 鈥淲e've started to work in the spatial transcriptomics area through this work too. It's a very new field, and there is a real need for new methods that help us make sense of the data. Interest is growing quickly and we鈥檝e gained a lot of visibility through this work.鈥�

Maria is currently working on further grant applications to partner with Mohit and some of the other experts she met at the symposium. One recent successful grant application is enabling Maria to partner with Professor Francesca Ciccarelli at the Francis Crick Institute and Dr Matteo Cereda at the University of Milan, to host a workshop on the spatial biology of cancer in September 2024. The team is also working on some manuscripts for submission to academic journals.

鈥淭his funding secured through the UCL Global Engagement Office really does address a gap in the field,鈥� Maria said. 鈥淭here aren鈥檛 many opportunities to establish international collaborations. Our different areas of expertise mean I wouldn鈥檛 normally meet people like Mohit at the type of conferences I attend. This is really good seed funding to develop ideas into bigger projects. I鈥檓 very grateful to have received it.鈥�

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