In a new study published in Nature Genetics titled, “The long-term effects of chemotherapy on normal blood cells,” researchers from the Wellcome Sanger Institute, the University of Cambridge, and Cambridge University Hospitals NHS Foundation Trust (CUH) have uncovered new patterns of DNA damage, or mutational signatures, associated with specific chemotherapy drugs. Identified by whole genome sequencing, the results could guide patient treatment with effective chemotherapies that have less harmful effects on healthy tissues.
“This study lays the groundwork for future research into the effects of chemotherapy on many other normal tissues, including multiple tissue sampling pre- and post-treatment, across a range of chemotherapies in a larger group of patients,” said Emily Mitchell, PhD, clinician at CUH and first author of the study. “This comprehensive view would reveal the full range of effects of different chemotherapies, and help us to optimize patient health in the long term.”
Chemotherapy is a systemic anti-cancer treatment that works throughout the body and can be administered as a single or combination of drugs. The treatment can have long-term side effects on healthy, non-cancerous tissues, and is associated with an increased risk of secondary cancers. However, there is limited understanding of the biological mechanisms underlying these side effects.
As part of the Cancer Grand Challenges team Mutographs, the researchers analyzed blood cell genomes from 23 patients of all ages who had been treated with a range of chemotherapies for various blood and solid cancers. Blood was chosen due to its ease in sampling and ability to be cultured in the laboratory. Additionally, the number of mutations in normal blood maintains strong consistency between individuals, providing a reliable baseline for evaluating chemotherapy effects.
Collectively, the patient group had been exposed to 21 drugs from all main chemotherapy classes, including alkylating agents, platinum agents, and anti-metabolites. The results were compared with genomic data from nine healthy people who had never received chemotherapy.
The researchers identified four new signatures found in chemotherapy-treated patients. For instance, the researchers found that some platinum agents, such as carboplatin and cisplatin, caused very high numbers of mutations, whereas other drugs in the same class, such as oxaliplatin, did not.
Results showed that many classes of chemotherapeutics, but not all, produce higher numbers of mutations in normal blood cells. For example, a three-year-old patient who was treated for neuroblastoma, a cancer of nerve tissue, had more than tenfold the number of mutations found in 80-year-old individuals who had never received chemotherapy.
In addition, the study investigated the effects of chemotherapy on hematopoietic stem cells, which are known to generate blood. In normal aging, the hematopoietic stem cells that produce blood decrease in diversity, due to the expansion of clones of cells that have driver mutations in cancer genes. Chemotherapy can accelerate this process, particularly in children whose blood appeared to prematurely age, which may increase the risk of secondary cancer later in life.
“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 optimization of future treatment plans to deliver effective chemotherapies with much fewer damaging side effects for patients,” said Jyoti Nangalia, PhD, group leader at the Wellcome Sanger Institute and co-lead author of the study.
Co-founded in 2020 by Cancer Research UK and the National Cancer Institute, Cancer Grand Challenges aims to provide awards of up to $25 million for interdisciplinary research teams whose ideas offer the greatest potential to advance bold cancer research and improve outcomes for people affected by cancer.
“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,” said David Scott, PhD, director of Cancer Grand Challenges. “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.”
The post Genetic Effects of Chemotherapy Revealed to Guide Cancer Treatment appeared first on GEN - Genetic Engineering and Biotechnology News.
“This study lays the groundwork for future research into the effects of chemotherapy on many other normal tissues, including multiple tissue sampling pre- and post-treatment, across a range of chemotherapies in a larger group of patients,” said Emily Mitchell, PhD, clinician at CUH and first author of the study. “This comprehensive view would reveal the full range of effects of different chemotherapies, and help us to optimize patient health in the long term.”
Chemotherapy is a systemic anti-cancer treatment that works throughout the body and can be administered as a single or combination of drugs. The treatment can have long-term side effects on healthy, non-cancerous tissues, and is associated with an increased risk of secondary cancers. However, there is limited understanding of the biological mechanisms underlying these side effects.
As part of the Cancer Grand Challenges team Mutographs, the researchers analyzed blood cell genomes from 23 patients of all ages who had been treated with a range of chemotherapies for various blood and solid cancers. Blood was chosen due to its ease in sampling and ability to be cultured in the laboratory. Additionally, the number of mutations in normal blood maintains strong consistency between individuals, providing a reliable baseline for evaluating chemotherapy effects.
Collectively, the patient group had been exposed to 21 drugs from all main chemotherapy classes, including alkylating agents, platinum agents, and anti-metabolites. The results were compared with genomic data from nine healthy people who had never received chemotherapy.
The researchers identified four new signatures found in chemotherapy-treated patients. For instance, the researchers found that some platinum agents, such as carboplatin and cisplatin, caused very high numbers of mutations, whereas other drugs in the same class, such as oxaliplatin, did not.
Results showed that many classes of chemotherapeutics, but not all, produce higher numbers of mutations in normal blood cells. For example, a three-year-old patient who was treated for neuroblastoma, a cancer of nerve tissue, had more than tenfold the number of mutations found in 80-year-old individuals who had never received chemotherapy.
In addition, the study investigated the effects of chemotherapy on hematopoietic stem cells, which are known to generate blood. In normal aging, the hematopoietic stem cells that produce blood decrease in diversity, due to the expansion of clones of cells that have driver mutations in cancer genes. Chemotherapy can accelerate this process, particularly in children whose blood appeared to prematurely age, which may increase the risk of secondary cancer later in life.
“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 optimization of future treatment plans to deliver effective chemotherapies with much fewer damaging side effects for patients,” said Jyoti Nangalia, PhD, group leader at the Wellcome Sanger Institute and co-lead author of the study.
Co-founded in 2020 by Cancer Research UK and the National Cancer Institute, Cancer Grand Challenges aims to provide awards of up to $25 million for interdisciplinary research teams whose ideas offer the greatest potential to advance bold cancer research and improve outcomes for people affected by cancer.
“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,” said David Scott, PhD, director of Cancer Grand Challenges. “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.”
The post Genetic Effects of Chemotherapy Revealed to Guide Cancer Treatment appeared first on GEN - Genetic Engineering and Biotechnology News.