Researchers have created a "metal detector" algorithm called PRRDetect to hunt down vulnerable tumours, in a development that could one day revolutionise the treatment of cancer.
In a paper published today (Thursday 10th April) in Nature Genetics, scientists funded by Cancer Research UK and the National Institute for Health and Care Research (NIHR) analysed the full DNA sequence of 4,775 tumours from seven types of cancer. Based at the University of Cambridge and NIHR Cambridge Biomedical Research Centre, they used that data from Genomics England's 100,000 Genomes Project to create an algorithm capable of identifying tumours with faults in their DNA that make them easier to treat.
The algorithm could one day help doctors figure out which patients are more likely to have successful treatment. That could pave the way for more personalised treatment plans that increase people's chances of survival.
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 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.
"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 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 tumours 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 tumours 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.
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 revolutionise how we approach cancer treatment. 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."
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."
The paper, titled "Redefined indel taxonomy reveals insights into mutational signatures", was published today (Thursday April 10th) in Nature Genetics*.
