Scientists develop a ‘metal detector’ to find cancer’s weak points

Our scientists have created an algorithm which can act as a ‘metal detector’ to pick out vulnerable tumours – a major breakthrough for personalised cancer treatments.  

PRRDetect, which was developed by researchers at the University of Cambridge, could one day be used to identify which cancer patients are most likely to benefit from immunotherapy.

It works by identifying patterns of mutations that appear in cancer cells when they are unable to repair errors in their DNA.  

“Cancers with faulty DNA repair are more likely to be treated successfully,” said Professor Serena Nik-Zainal, who led the first study into the new algorithm. “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 study, which we funded with the National Institute for Health and Care Research, was published today in Nature Genetics.

The power of genomics 

PRRDetect is a major step forward in using genomics – the study of all the information in a person’s DNA – to unlock better insights into cancer.  

Before now, genomic sequencing (or DNA reading) tests have mostly been used to look for specific cancer-driving mutations (like changes to BRCA genes) that doctors can target with specific drugs. The new algorithm goes further by looking for patterns of mutations, or ‘mutational signatures’, that signify something deeper. 

For this particular study, researchers carefully examined patterns in DNA undergoing indel mutations. This type of mutation involves nucleotides (or letters of DNA code) being incorrectly inserted or deleted in a cell’s DNA sequence.  

By investigating these indel mutations across almost 5,000 tumours, researchers found some unusual patterns that pointed to ‘post replicative repair dysfunction’ or PRRd – essentially meaning that some of these cells had faulty repair mechanisms. They then used that information to develop their PRRDetect metal detector, which searches genome sequences for PRRd-linked mutation patterns. 

Because PRRd tumours are more sensitive to immunotherapy, which guides the body’s own immune system to attack cancerous cells, the research team believe their new tool could help turn genomic insights into new ways of helping patients. 

“Genomic sequencing is now far faster and cheaper than ever before,” explained Nik-Zainal, the University of Cambridge’s Professor of Genomic Medicine and Bioinformatics. “We are getting closer to the point where getting your tumour 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 tumour might respond to treatment. This is especially important in cancers where survival is poorer, like lung cancer and brain tumours.” 

Making personalised treatment a reality 

As well as investigating genomic data from lung and brain tumours, the team also looked at bowel, endometrial, skin, bladder and stomach cancers. There was already some evidence that PRRd was more common in these cancer types, but PRRDetect could be the first effective tool for spotting it.  

The research team are now focussing on carrying out clinical trials to test how well they can use PRRDetect to predict people’s response to immunotherapy. They’re also planning a similar genomic analysis across 20 cancer types, hopefully paving the way for more powerful breakthroughs.  

Today’s study also uncovered some new clues about the possible causes of cancer.  

Ten of the indel mutation patterns spotted by the team were linked to known causes such as tobacco usage and UV light exposure, but 19 others hadn’t been identified before. These may point to causes of cancers which we do not fully understand yet, or growth mechanisms that could be vulnerable to different types of treatment. 

Dr Iain Foulkes, our Executive Director of Research and Innovation, summed up what the overall findings could mean for people with cancer. 

“Genomic medicine will revolutionise how we approach cancer treatment,” he said. “We can now get full readouts of tumour 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 personalised treatment for cancer a reality for many more patients in the future. Personalising treatment is much more likely to be successful, ensuring more people can live longer, better lives free from the fear of cancer.”