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Cancer drugs can vary widely in genetic damage caused by healthy blood, scientists discovered in a groundbreaking study that uncovers potential new pathways to select treatments with fewer harmful long-term side effects.
This study suggests that DNA analysis may be important one day to identify drugs that are at a low risk of causing adverse outcomes such as secondary tumors and organ damage, especially for children.
“We are always looking for better ways to treat and minimize the side effects of toxic and systemic treatment,” said Ir Miks Tratton, co-lead author of the UK Welcome Sanger Institute.
“We hope that genomic information from this and future research will guide chemotherapy selection and adoption in clinical practice.”
The results published in Nature Genetics on Tuesday are pioneering efforts to chart the genetic effects of systemic chemotherapy on normal tissues.
Cancer is caused by cellular DNA mutations that can be inherited, caused by environmental factors, or that can occur randomly. The study delves into genetic reasons why chemotherapeutic drugs may increase the risk of developing secondary tumors in those being treated.
The research team, including members of Cambridge University and its hospital trust, sequenced the blood cell genomes of 23 patients treated with chemotherapy for various cancers. They compared the results from the blood of nine healthy people who had never received chemotherapy.
Of the 21 drugs studied, it caused mutations and premature aging in healthy blood, although not all, researchers found. A 3-year-old patient receiving treatment for neural tissue cancer had more mutations than is commonly seen in 80-year-old children who had never received chemotherapy.
Scientists have discovered a major difference in mutational effects, like those with clearly similar chemotherapeutic drugs, based on the precious metal platinum. In treatment, carboplatin and cisplatin caused a huge number of mutations, but oxaliplatin was not.
The study’s limitations include only a small number of participants and a range of certain types of cancer and chemotherapy drugs, the researchers said.
The task failed to address several potentially important factors, such as how the body interacted with the drug, they added.
David Scott, director of the International Cancer Grand Challenges Initiative, despite the advent of new “precision” therapies, remained a “critical way” for combating cancer.
“Studies like this are important to help scientists improve future cancer treatments. They are not only more effective, but also safe for those living with cancer,” said Scott, whose organization funded the job.
Arena Pans, a senior lecturer in genetics at the University of Hertfordshire, said the study raised prospects for better tailored treatments, but other considerations remain important in drug selection.
“The complete outcome of chemotherapy and the insights into the different drug characteristics revealed by this study are key steps to moving towards a more targeted approach to a more targeted treatment approach,” Pans said.
“However, most importantly, the use of different agents must be considered in parallel with its effectiveness, the context of the disease, and the background of the genome of the individual patient.”
