Cancer treatments can significantly differ in the genetic harm they inflict on healthy blood cells, according to a groundbreaking study that uncovers new possibilities for selecting therapies with fewer long-term adverse effects.
The findings indicate that someday, analyzing DNA may play a vital role in identifying medications that pose a lower chance of severe side effects, like secondary tumors or organ damage, which is particularly crucial for younger patients.
“We’re always searching for better methods to administer therapies while reducing the toxic effects of systemic treatments,” remarked Sir Mike Stratton, a co-lead author and professor at the UK’s Wellcome Sanger Institute.
“I’m optimistic that the genomic insights from this and forthcoming research will help steer chemotherapy decisions and their use in clinical settings.”
The study, published in Nature Genetics on Tuesday, is an innovative attempt to map the genetic repercussions of systemic chemotherapy on normal tissues.
Cancers arise from DNA mutations in cells, which may be inherited, induced by environmental influences, or happen randomly. This research investigates potential genetic reasons why chemotherapy might increase the risk of developing additional tumors.
The research group, which includes members from Cambridge University and its hospital trust, sequenced blood cell genomes from 23 patients undergoing chemotherapy for various cancers. They contrasted these results with blood samples from nine healthy individuals who had never undergone chemotherapy.
Researchers found that many of the 21 chemotherapy drugs examined caused mutations and signs of accelerated aging in healthy blood, but not all did. For instance, a three-year-old patient treated for a nerve tissue cancer had a mutation rate typical of an 80-year-old who had never received chemo.
They noted notable variances in mutational effects among seemingly similar chemotherapy drugs, particularly those based on platinum. Treatments like carboplatin and cisplatin were linked to a high mutation count, while oxaliplatin did not show this effect.
However, the study has its limitations, including a small participant pool and its focus on only certain cancers and chemotherapy agents. The researchers also indicated that they couldn’t explore some essential factors, like how an individual’s body might react to the drugs.
Despite advancements in “precision” treatments, systemic chemotherapy remains a fundamental strategy for addressing cancers, noted David Scott, director of the international Cancer Grand Challenges initiative.
“Research like this is vital for aiding scientists in refining cancer treatments—making them not only more effective but also safer for those living with cancer,” Scott explained, highlighting that his organization supported this study.
The research opens doors to better-personalized treatments, but Alena Pance, a senior lecturer in genetics at the University of Hertfordshire, stressed that other factors remain essential in drug selection.
“This study provides significant insights into the overall impact of chemotherapy and the unique characteristics of different agents, marking an important step towards a more targeted therapeutic approach,” Pance stated.
“However, it’s crucial to consider the different medications alongside their effectiveness, the context of the disease, and the individual genomic background of patients.”
