Researchers from the University of Cambridge and the NIHR Cambridge Biomedical Research Centre have created an algorithm that finds vulnerable cancer tumours
The new tool, PRRDetect, identifies cancer tumours with defective DNA repair mechanisms, potentially transforming how doctors determine which patients are more likely to respond successfully to cancer treatments. The study paper was published in Nature Genetics.
Researchers analysed the complete DNA sequence of 4,775 tumours
The researchers analysed the complete DNA sequence of 4,775 tumours from seven types of cancer. They used Genomics England’s 100,000 Genomes Project data to create an algorithm to identify cancer tumours with DNA faults.
The team looked for patterns in DNA created by indel mutations. This is when letters are inserted or deleted from the typical DNA sequence. They found unusual patterns of indel mutations in cancers with faulty DNA repair mechanisms, known as post-replicative repair dysfunction (PRRd). This data allowed the researchers to develop the algorithm and identify cancer tumours effectively.
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 help doctors better tailor treatments to individual patients.
Revolutionising cancer treatment with genomes
PRRd tumours are more sensitive to immunotherapy, a cancer treatment that uses the body’s immune system to attack cancer cells.
The researchers looked at cancers with a higher proportion of cancer tumours with PRRd, including bowel, brain, endometrial, skin, lung, bladder and stomach cancers. They analysed the whole genome sequences of these.
It identified 37 different patterns of indel mutations across the seven cancer types included in this study. Of these, it found:
- Ten were already linked to known causes of cancer, such as smoking and exposure to UV light.
- Eight were linked to PRRd.
- Nineteen were new and could be linked to causes of cancer not fully understood 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.”
