Genetic analysis of samples collected from patients treated at Addenbrooke’s Hospital has shown the long-term effects that chemotherapy has on the body. Researchers say the findings could inform the development of kinder treatments.
Published today (1 July) in Nature Genetics, the study included samples from 23 patients, aged between three and 80 years, that had been treated for various different cancers using chemotherapies. 22 of the patients were treated at Addenbrooke’s and overall 21 different chemotherapy drugs were used. This is the first systematic study of the effect that chemotherapy has on the genetics of healthy cells.
Given that, for many cancers, chemotherapy drugs can be switched with other agents to achieve similar results, we hope such genomic data will guide the optimisation of future treatment plans to deliver effective chemotherapies with much fewer damaging side effects for patients.
Dr Jyoti Nangalia, co-lead author at the Wellcome Sanger Institute and consultant haematologist at CUH
Around 10% of people in the UK are thought to have had chemotherapy at some point in their lifetime. While it is a highly effective approach for treating cancer, it has many notable side effects and causes genetic damage that can increase the risk of developing secondary cancers later in life.
Chemotherapy drugs can be used individually to treat cancer but are often used in combinations allowing them to have a stronger effect on the target cancer.
The study used whole genome sequencing (WGS) to show that many, but not all, chemotherapies cause genetic damage and premature ageing in healthy blood cells. The results also revealed distinct patterns of genetic changes that could be linked to particular chemotherapy drugs.
For the first time, we have taken a systematic view of the genetic effects of chemotherapy on healthy tissues – in this case, blood. We find that some, but not all chemotherapies cause genetic mutations and premature ageing in normal blood.
Dr Emily Mitchell, first author at the Wellcome Sanger Institute and clinician at CUH
Samples from the 23 people treated using chemotherapy were compared to samples from 6 healthy volunteers. The analysis found that a three-year-old that had been treated had more genetic changes in her blood than an 80-year-old that had never had chemotherapy.
The scientists suggest that genomic data could help in choosing chemotherapies for children to minimise premature ageing and monitor further genetic changes later in life. They also hope that these results can be used to design better cancer treatments that cause less damage to healthy cells.
While many cancers can now be targeted using precision therapies, chemotherapy remains a key way to treat some cancers and saves many lives every year, so it’s vital that patients continue with the treatment recommended by their doctor. At the same time, studies like this are crucial for helping scientists improve cancer treatments in the future – making them not only more effective but also safer for people living with cancer.
David Scott, Director of Cancer Grand Challenges
The study is supported by the Cancer Grand Challenges and was led by researchers at Cambridge University Hospitals NHS Foundation Trust (CUH), the Wellcome Sanger Institute and the University of Cambridge.
The study focused on blood cells because the normal number of genetic changes in healthy blood is very consistent between people, which helped to identify changes resulting from different chemotherapies. Blood cells are also very easy to collect and study.
Professor Sir Mike Stratton, Mutographs team lead and co-lead author at the Wellcome Sanger Institute, said: “We are constantly on the lookout for better ways of giving therapy and minimising the side effects of toxic, systemic treatments. I’m hopeful that the genomic information from this and future studies will guide choices of chemotherapies, and their adoption in clinical practice.”
Find out more about this story at the Wellcome Sanger Institute.