Cambridge researchers have developed a ‘metal detector’ algorithm that can pinpoint vulnerable tumors—a breakthrough that could significantly improve cancer treatment in the future.
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In a paper published today in Nature Genetics, scientists from the University of Cambridge and the NIHR Cambridge Biomedical Research Centre analyzed the full DNA sequences of 4775 tumors across seven cancer types. Using data from Genomics England’s 100,000 Genomes Project, the team developed an algorithm that can identify tumours with specific DNA repair faults that make them more responsive to treatment.
The algorithm, called PRRDetect, could help doctors identify patients who are more likely to benefit from certain therapies—enabling more personalized treatment plans and potentially improving survival rates.
The research was funded by Cancer Research UK and the National Institute for Health and Care Research (NIHR).
Genomic sequencing is now far faster and cheaper than ever before. We are getting closer to the point where getting your tumor sequenced will be as routine as a scan or blood test.
Serena Nik-Zainal, Study Lead Author and, Early Cancer Institute, University of Cambridge
“To use genomics most effectively in the clinic, we need tools which give us meaningful information about how a person’s tumor might respond to treatment. This is especially important in cancers where survival is poorer, like lung cancer and brain tumors,” added Nik-Zainal.
“Cancers with faulty DNA repair are more likely to be treated successfully. PRR Detect helps us better identify those cancers and, as we sequence more and more cancers routinely in the clinic, it could ultimately help doctors better tailor treatments to individual patients,” further added Nik-Zainal.
The team focused on patterns in DNA caused by ‘indel’ mutations—instances where letters are inserted into or deleted from the genetic code.
They discovered distinctive indel mutation patterns in cancers with defective DNA repair mechanisms, a condition known as post-replicative repair dysfunction (PRRd). Using these insights, they designed PRRDetect to spot tumors with this fault from a complete DNA sequence.
Tumors with PRRd are more likely to respond to immunotherapy, a type of treatment that harnesses the body’s immune system to fight cancer. The researchers hope the algorithm can serve as a kind of ‘metal detector’—highlighting patients most likely to benefit from this approach.
The study builds on previous work by Professor Nik-Zainal, who led an extensive analysis of cancer genomes that uncovered hidden patterns of mutations linked to the disease.
This latest research focused on cancer types with a higher proportion of PRRd tumors, including bowel, brain, endometrial, skin, lung, bladder, and stomach cancers. Whole genome sequences were provided by the 100,000 Genomes Project—a landmark initiative led by Genomics England and NHS England, which sequenced 100,000 genomes from around 85,000 NHS patients affected by cancer or rare diseases.
The study identified 37 distinct indel mutation patterns across the seven cancer types. Ten were linked to known cancer causes such as smoking or UV exposure. Eight were associated with PRRd, and the remaining 19 were newly discovered—potentially tied to unknown causes or internal cellular mechanisms that break down during cancer development.
Genomic medicine will revolutionize how we approach cancer treatment. We can now get full readouts of tumor DNA much more easily, and with that comes a wealth of information about how an individual’s cancer can start, grow and spread.
Dr. Iain Foulkes, Executive Director, Research and Innovatin, o Cancer Research UK
“Tools like PRR Detect are going to make personalized treatment for cancer a reality for many more patients in the future. Personalizing treatment is much more likely to be successful, ensuring more people can live longer, better lives free from the fear of cancer,” added Foulkes.
NIHR Scientific Director, Mike Lewis, stated, “Cancer is a leading cause of death in the UK so it's impressive to see our research lead to the creation of a tool to determine which therapy will lead to a higher likelihood of successful cancer treatment.”
Chief Scientific Officer at Genomics England, Professor Matt Brown added, “Genomics is playing an increasingly important role in healthcare and these findings show how genomic data can be used to drive more predictive, preventative care leading to better outcomes for patients with cancer. The creation of this algorithm showcases the immense value of whole genome sequencing not only in research but also in the clinic across multiple diverse cancer types in advancing cancer care.”
Journal Reference:
Koh, G. C. C, et al. (2025) A redefined InDel taxonomy provides insights into mutational signatures. Nature Genetics. doi.org/10.1038/s41588-025-02152-y