New “Metal Detector” Algorithm Could Revolutionize Cancer Treatment

PRRDetect is a new algorithm that identifies tumors with faulty DNA repair, helping doctors tailor cancer treatments more effectively. It marks a major step in using genomics for personalized cancer therapy.

Researchers have developed a highly accurate algorithm, named PRRDetect, designed to identify tumors with specific DNA repair defects, an advancement that could significantly improve cancer treatment.

In a study in Nature Genetics, scientists supported by Cancer Research UK and the National Institute for Health and Care Research (NIHR) analyzed the complete DNA sequences of 4,775 tumors across seven cancer types. The research team, based at the University of Cambridge and the NIHR Cambridge Biomedical Research Centre, used genomic data from Genomics England’s 100,000 Genomes Project to build PRRDetect.

This algorithm pinpoints tumors with particular DNA repair weaknesses, which often respond better to certain treatments. In the future, PRRDetect could help clinicians identify which patients are more likely to benefit from targeted therapies, enabling more personalized and effective treatment plans, and potentially improving survival rates.

Professor of Genomic Medicine and Bioinformatics at the University of Cambridge, NIHR Research Professor and lead author of the study, Professor Serena Nik-Zainal, said: “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.

“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.

“Cancers with faulty DNA repair are more likely to be treated successfully. PRRDetect 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.”

The Science Behind the Tool

The research team looked for patterns in DNA created by so-called “indel” mutations, in which letters are inserted or deleted from the normal DNA sequence.

They found unusual patterns of “indel” mutations in cancers which had faulty DNA repair mechanisms – known as “post-replicative repair dysfunction” or PRRd. Using this information, the scientists developed an algorithm called PRRDetect which allows them to identify tumours that have PRRd from a full DNA sequence.

PRRd tumors are more sensitive to immunotherapy, a type of cancer treatment that uses the body’s own immune system to attack cancer cells. The scientists hope that the PRRd algorithm could act like a “metal detector” to allow them to identify patients who are more likely to have successful treatment with immunotherapy.

The study follows from a previous “archaeological dig” of cancer genomes carried out by Professor Serena Nik-Zainal and funded by Cancer Research UK. This “dig” examined the genomes of tens of thousands of people and revealed previously unseen patterns of mutations which are linked to cancer. This time, Professor Nik-Zainal and her team looked at cancers which have a higher proportion of tumors with PRRd. These include bowel, brain, endometrial, skin, lung, bladder and stomach cancers. Whole genome sequences of these cancers were provided by the 100,000 Genomes Project – a pioneering study led by Genomics England and NHS England which sequenced 100,000 genomes from around 85,000 NHS patients affected by rare diseases or cancer.

New Mutation Patterns Identified

The study identified 37 different patterns of indel mutations across the seven cancer types included in this study. Ten of these patterns were already linked to known causes of cancer, such as smoking and exposure to UV light. Eight of these patterns were linked to PRRd. The remaining 19 patterns were new and could be linked to causes of cancer that are not fully understood yet or mechanisms within cells that can go wrong when a cell becomes cancerous.

Executive Director of Research and Innovation at Cancer Research UK, Dr Iain Foulkes, said: “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.

“Tools like PRRDetect 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.”

NIHR Scientific Director, Professor Mike Lewis, said: “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.

“The NIHR is at the forefront of developing cancer treatments as we aim to meet the Secretary of State’s goal of reducing the UK’s major killers. This is yet another example of how we can work together with partners like Cancer Research UK and lead research that improves people’s health outcomes, allows them to live longer and live better.”

Chief Scientific Officer at Genomics England, Professor Matt Brown, said: “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.”

Reference: “A redefined InDel taxonomy provides insights into mutational signatures” by Gene Ching Chiek Koh, Arjun Scott Nanda, Giuseppe Rinaldi, Soraya Boushaki, Andrea Degasperi, Cherif Badja, Andrew Marcel Pregnall, Salome Jingchen Zhao, Lucia Chmelova, Daniella Black, Laura Heskin, João Dias, Jamie Young, Yasin Memari, Scott Shooter, Jan Czarnecki, Matthew Arthur Brown, Helen Ruth Davies, Xueqing Zou and Serena Nik-Zainal, 10 April 2025, Nature Genetics.
DOI: 10.1038/s41588-025-02152-y

Funding: Cancer Research UK, National Institute for Health Research