Whole genome sequencing could be used to improve cancer treatments
Posted: 30 September 2019 | Victoria Rees (Drug Target Review) | No comments yet
Researchers have used whole genome sequencing to analyse breast cancers and reveal which are more responsive to treatments, which could improve the development of oncologic therapies.
A study has found that whole genome sequencing (WGS) of tumour cells could be used to improve cancer treatments.
The team, led by the University of Cambridge, UK used the technique. This involves analysing the entire genetic blueprint of a cancer cell and comparing it to a patient’s healthy cells to identify how the DNA has mutated, allowing the factors influencing the growth of the tumour to be revealed.
The researchers utilised data from the SCAN-B project, which recruits women in Sweden with triple negative breast cancer.
“Having a complete cancer genome map for each patient helps us to understand what has caused each patient’s tumour and treat each individual more effectively. Previously, it was like going on a voyage with only a limited map, but now, with WGS we have a much better, more detailed map and know the best route to reach our destination,” explains Dr Serena Nik-Zainal from the Medical Research Council Cancer Unit at the University of Cambridge, who led the study.
…WGS indicated the mechanisms driving these tumours, which in turn could help inform the development of new drugs”
The team applied a machine learning algorithm called HRDetect, developed by the researchers previously to identify tumours with signatures caused by mutations in the BRCA1 or BRCA2 genes; a variant of these greatly increases the risk of breast cancer.
Using the results, the team categorised each patient as either high, intermediate or low scoring. Those with high scores had the best outcomes using current treatments.
The researchers say that surprisingly, those with intermediate scores had the poorest outcomes. Current triple negative breast cancer treatments had limited effectiveness suggesting that new approaches would be necessary to tackle these cancers. However, the genetic changes and signatures revealed through WGS indicated the mechanisms driving these tumours, which in turn could help inform the development of new drugs, say the team.
The WGS profile for tumours of patients with the lowest scores suggested biological abnormalities that could potentially be targeted by existing drugs or treatments currently going through clinical trials.
“Importantly, this approach also gives us clues to some of the mechanisms that are going wrong in the poor-outcome tumours and hence how we might treat those tumours differently or how we might develop new drugs,” says first author Dr Johan Staaf from the Department of Clinical Sciences, Lund University, Sweden.
The results were published in Nature Medicine.
Analytical Techniques, Genetic Analysis, Genomics, Personalised Medicine, Research & Development, Screening, Sequencing
Triple-negative breast cancer
Lund University, University of Cambridge
Dr Johan Staaf, Dr Serena Nik-Zainal