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Cancer drugs can vary sharply in the genetic damage they cause to healthy blood, scientists have found, in a landmark study that reveals potential new paths to choosing treatments with fewer harmful long-term side effects.
The research suggests DNA analysis could one day be important to identify medicines with a lower risk of causing adverse outcomes such as secondary tumours or organ damage, especially for children.
“We are constantly on the lookout for better ways of giving therapy and minimising the side effects of toxic, systemic treatments,” said Sir Mike Stratton, co-lead author of the paper and a professor at the UK’s Wellcome Sanger Institute.
“I’m hopeful that the genomic information from this and future studies will guide choices of chemotherapies, and their adoption in clinical practice.”
The results, published in the journal Nature Genetics on Tuesday, are a pioneering effort to chart the genetic effects of systemic chemotherapy on normal tissues.
Cancers are caused by cell DNA mutations that can be inherited, triggered by environmental factors or occur at random. The study delves into possible genetic reasons why chemotherapy drugs raise the risk of developing secondary tumours to the one being treated.
The research team, including members from Cambridge university and its hospitals trust, sequenced blood cell genomes from 23 patients treated with chemotherapies for a range of cancers. They compared the results with those from the blood of nine healthy people who had never received chemotherapy.
Many — but not all — of the 21 drugs studied caused mutations and premature ageing in healthy blood, the researchers found. One three-year-old patient being treated for a nerve tissue cancer had more mutations then typically found in 80-year-olds who had never received chemotherapy.
The scientists found big differences in mutational effects in apparently similar chemotherapy drugs, such as those based on the precious metal platinum. While the treatments carboplatin and cisplatin caused very high numbers of mutations, oxaliplatin did not.
The study’s limitations included the small number of participants and its coverage of only certain types of cancers and chemotherapy medicines, the researchers said.
The work was unable to address some potentially important factors, such as how the body interacted with the drug, they added.
Systemic chemotherapy remained a “key way” to combat cancers despite the emergence of new “precision” therapies, said David Scott, director of the international Cancer Grand Challenges initiative.
“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,” said Scott, whose organisation funded the work.
The research raised the prospect of better tailored treatments but other considerations would still be crucial in choosing drugs, said Alena Pance, senior lecturer in genetics at the University of Hertfordshire.
“The insight into the full consequences of chemotherapy and the characteristics of different agents revealed by this study is a significant step to move towards a more targeted therapeutic approach,” Pance said.
“Most importantly, however, the use of different agents has to be considered in parallel with their efficacy and in the context of the disease, as well as the genomic background of the individual patients.”
