Programme – which created biological map of tumour – shows potential to be beneficial for other tumours, researchers believe
Newly discovered drug combinations could be more effective at treating the most common type of bowel cancer, Irish researchers have found.
Using artificial intelligence, a research team led by RCSI University of Medicine and Health Sciences and London’s Institute of Cancer Research (ICR) have identified new treatment approaches for microsatellite stable (MSS) colorectal cancer.
The subtype accounts for 80-85 per cent of all bowel cancer cases. Using 2,000 of these patient tumour samples, the researchers discovered particular vulnerabilities that they hope can be exploited by new therapy methods.
“Patients with MSS RAS-mutant metastatic colorectal cancer urgently need better treatment options, particularly when their disease no longer responds to standard therapy,” said Prof Annette Byrne, Head of the RCSI Precision Cancer Medicine Group.
“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.”
Led by Prof Byrne and ICR Prof Anguraj Sadanandam, the research team analysed genetic, metabolic protein and clinical data in 2,000 patient tumour samples using an AI tool they developed called iPhenMap.
The programme was able to create a biological map of the tumour, uncovering previously unrecognised ways in which the cancer cells divide, grow, adapt and interact with their environment.
Through this work, the researchers 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.
After finding new tumour vulnerabilities and testing them in laboratory models, they showed that certain drug combinations could work well to target and treat the cancer.
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.
“A major strength of this research is the scale and diversity of the dataset, which was only possible through collaboration with European partners,” said Prof Sadanandam.
“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.”
The research is published in the journal Cancer Cell. It was funded by the European Union’s Horizon 2020 Research and Innovation Programme through funding awarded to the COLOSSUS project, and by a Research Ireland Project Award to Prof Byrne.