An innovative algorithm, likened to a “metal detector” for tumours, has been developed by researchers at the University of Cambridge to identify cancers most likely to respond to immunotherapy. The tool, named PRRDetect, analyses the full DNA sequence of tumours, offering the potential to revolutionise cancer treatment and move it towards a more personalised approach.
The research, published in Nature Genetics, involved analysing the genomes of 4,775 tumours across seven different cancer types, utilising data from Genomics England’s 100,000 Genomes Project. Scientists focused on identifying patterns of DNA damage – specifically ‘indel’ mutations where letters are inserted or deleted – that indicate a weakness in the tumour’s ability to repair its DNA.
These tumours with faulty DNA repair mechanisms, known as ‘post-replicative repair dysfunction’ (PRRd), are known to be particularly sensitive to immunotherapy – a treatment that harnesses the body’s own immune system to fight cancer. PRRDetect is designed to quickly and accurately identify these PRRd tumours, enabling doctors to select patients most likely to benefit from immunotherapy.
“We are getting closer to the point where getting your tumour sequenced will be as routine as a scan or blood test,” explained lead author Professor Serena Nik-Zainal from the Early Cancer Institute at the University of Cambridge. “To use genomics most effectively in the clinic, we need tools which give us meaningful information about how a person’s tumour might respond to treatment.”
The algorithm identified 37 distinct patterns of indel mutations across bowel, brain, endometrial, skin, lung, bladder and stomach cancers. While some patterns were linked to known causes, like smoking or UV exposure, 19 were entirely new, offering potential insights into previously unknown drivers of cancer.
Experts believe PRRDetect will be instrumental in tailoring treatments for individuals and improving outcomes. Dr Iain Foulkes, executive director of research and innovation at Cancer Research UK, stated the tool would make “personalised treatment for cancer a reality for many more patients in the future.”
The research was supported by funding from Cancer Research UK and the National Institute for Health and Care Research. Genomics England’s chief scientific officer, Professor Matt Brown, highlighted the increasing role of genomics in healthcare, anticipating the use of such tools in improving predictive and preventative care, leading to better outcomes for cancer patients.
