A major new research study has identified potential new ways to treat the most common type of bowel cancer, affecting more than 39,000 people in the UK each year.
The study, conducted by an international research team led by The Institute of Cancer Research, London and RCSI University of Medicine and Health Sciences, provides a clear roadmap for repurposing existing drugs and developing new ones, to create more effective, personalised treatments for thousands of patients who currently have limited options.
Challenging to treat cancer
Of the 48,213 new bowel cancer cases diagnosed annually in the UK, Microsatellite stable (MSS) colorectal cancer accounts for 80 to 85 per cent of these, but remains challenging to treat, with limited response to many newer therapies. Trials combining chemotherapy with newer targeted drugs or immunotherapies have delivered only modest improvements over current standard treatments.
Now, researchers have discovered vulnerabilities in these tumours and have identified the drug combinations – including drugs already approved to treat other tumour types – that could be used to target them, leading to more effective treatments for bowel cancer.
Using AI to analyse vast amounts of data
Using 2,000 patient tumour samples, the researchers analysed genetic, metabolic protein and clinical data with the help of artificial intelligence (AI) tools, revealing previously unrecognised ways in which the cancer cells divide, grow, adapt and interact with their environment.
To do this, the team developed an AI approach called iPhenMap, which can create a biological map of the tumour. Using this map, they were able to spot connections between the different elements of the tumour – such as the genetic and metabolic features – that have been missed in previous studies that looked at the data in isolation.
Importantly, they found previously unidentified vulnerabilities in the tumours. They then tested these vulnerabilities in laboratory models and showed that certain drug combinations could work well to target them and treat the cancer.
Identifying drugs to target vulnerabilities
For example, the targeted drug trametinib – approved to treat various cancers including melanoma, lung cancer, and thyroid cancer, with a specific mutation – was shown to significantly reduce tumour growth and extend survival in the laboratory models when combined with other drugs.
The researchers hope this work will accelerate the path to clinical testing of new treatment strategies for bowel cancer, using drugs which have already been developed and approved. In addition, the team believe their AI approach could be used to identify more effective drugs for other tumour types.
Exposing connections that would otherwise be missed
Professor Annette Byrne, Head of the Precision Cancer Medicine Group, RCSI University of Medicine and Health Sciences, said: “Patients with MSS RAS-mutant metastatic colorectal cancer urgently need better treatment options, particularly when their disease no longer responds to standard therapy.
“While these findings remain preclinical, they highlight promising therapeutic opportunities and provide a strong foundation for further development. The next step will be to identify the biological features that predict response and determine how these approaches can be advanced safely towards clinical evaluation.”
Professor Anguraj Sadanandam Group Leader, Systems and Precision Cancer Medicine Group, The Institute of Cancer Research, London, said: “A major strength of this research is the scale and diversity of the dataset, which was only possible through collaboration with European partners. By bringing together data from patients across multiple countries and integrating DNA, RNA, epigenetic, protein, metabolic, single-cell and clinical data at this scale, we were able to expose connections between tumour biology and therapeutic dependency that would otherwise be missed.
“AI and machine learning will increasingly help cancer researchers to bring these complex data together, not just to classify tumours, but to understand how they behave, identify their vulnerabilities and guide the development and repurposing of treatments, so that patients can live longer and healthier lives.”
Ensuring the patient voice was embedded throughout the project and that the findings were disseminated in an accessible format was a priority.
This research was funded by the European Union’s Horizon 2020 Research and Innovation Programme through funding awarded to the COLOSSUS project (www.colossusproject.eu), and by a Research Ireland Project Award to Professor Byrne. COLOSSUS, led by Professor Byrne, brings together leading European and international academics, clinicians, private sector and not-for-profit partners.
