Chemotherapy Side-Effects: Not All DNA Damage Is Equal

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. T...

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Published inCancers Vol. 14; no. 3; p. 627
Main Authors van den Boogaard, Winnie M C, Komninos, Daphne S J, Vermeij, Wilbert P
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 26.01.2022
MDPI
Subjects
20th century
Aging
Antibiotics
Apoptosis
Cancer
Cancer therapies
Cell cycle
Cell differentiation
Cell division
Chemotherapy
Children
Creatinine
Deoxyribonucleic acid
Detoxification
DNA
DNA biosynthesis
DNA damage
DNA repair
Drug dosages
Genomes
Genomic instability
Genotoxicity
Kidneys
Leukemia
Liver
Lymphoma
Patients
Pediatrics
Quality of life
Radiation therapy
Review
Sarcoma
Side effects
Toxicity
Transcription
Tumors
Urine
cancer treatment
cancer survivors
chemotherapy
premature aging
DNA damage
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Abstract Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark of both cancer and aging. However, there are numerous types of chemotherapeutic drugs that are genotoxic and interfere with DNA metabolism in different ways, each with their own biodistribution, kinetics, and biological fate. Depending on the type of DNA lesion produced (e.g., interference with DNA replication or RNA transcription), the organ or cell type inflicted (e.g., cell cycle or differentiation status, metabolic state, activity of clearance and detoxification mechanisms, the cellular condition or micro-environment), and the degree of exposure, outcomes of cancer treatment can largely differ. These considerations provide a conceptual framework in which different classes of chemotherapeutics contribute to the development of toxicities and accelerated aging of different organ systems. Here, we summarize frequently observed side-effects in (pediatric) ex-cancer patients and discuss which types of DNA damage might be responsible.
AbstractList Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark of both cancer and aging. However, there are numerous types of chemotherapeutic drugs that are genotoxic and interfere with DNA metabolism in different ways, each with their own biodistribution, kinetics, and biological fate. Depending on the type of DNA lesion produced (e.g., interference with DNA replication or RNA transcription), the organ or cell type inflicted (e.g., cell cycle or differentiation status, metabolic state, activity of clearance and detoxification mechanisms, the cellular condition or micro-environment), and the degree of exposure, outcomes of cancer treatment can largely differ. These considerations provide a conceptual framework in which different classes of chemotherapeutics contribute to the development of toxicities and accelerated aging of different organ systems. Here, we summarize frequently observed side-effects in (pediatric) ex-cancer patients and discuss which types of DNA damage might be responsible.Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark of both cancer and aging. However, there are numerous types of chemotherapeutic drugs that are genotoxic and interfere with DNA metabolism in different ways, each with their own biodistribution, kinetics, and biological fate. Depending on the type of DNA lesion produced (e.g., interference with DNA replication or RNA transcription), the organ or cell type inflicted (e.g., cell cycle or differentiation status, metabolic state, activity of clearance and detoxification mechanisms, the cellular condition or micro-environment), and the degree of exposure, outcomes of cancer treatment can largely differ. These considerations provide a conceptual framework in which different classes of chemotherapeutics contribute to the development of toxicities and accelerated aging of different organ systems. Here, we summarize frequently observed side-effects in (pediatric) ex-cancer patients and discuss which types of DNA damage might be responsible.
Simple SummaryThe number of children and adults with cancer that are completely cured is still increasing thanks to effective anti-cancer therapy, but they may be confronted with the negative lasting effects of the treatment later in life. In this review, we provide an overview of major clinical symptoms and toxic side-effects observed in cancer survivors. We describe which types of anti-cancer treatments—primarily DNA-damaging chemotherapeutics—might cause these toxicities and what the (potential) underlying mechanisms are. These treatments not only damage cancer cells in their attempt at tumor killing but also harm healthy cells and tissues. Observations of side-effects in cancer patients and survivors strengthen the hypothesis that the primary induced DNA damage can lead to varying toxicities while also accelerating features of aging, depending on type and dose of chemotherapeutic, clearing method, and affected organ.AbstractRecent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark of both cancer and aging. However, there are numerous types of chemotherapeutic drugs that are genotoxic and interfere with DNA metabolism in different ways, each with their own biodistribution, kinetics, and biological fate. Depending on the type of DNA lesion produced (e.g., interference with DNA replication or RNA transcription), the organ or cell type inflicted (e.g., cell cycle or differentiation status, metabolic state, activity of clearance and detoxification mechanisms, the cellular condition or micro-environment), and the degree of exposure, outcomes of cancer treatment can largely differ. These considerations provide a conceptual framework in which different classes of chemotherapeutics contribute to the development of toxicities and accelerated aging of different organ systems. Here, we summarize frequently observed side-effects in (pediatric) ex-cancer patients and discuss which types of DNA damage might be responsible.
Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark of both cancer and aging. However, there are numerous types of chemotherapeutic drugs that are genotoxic and interfere with DNA metabolism in different ways, each with their own biodistribution, kinetics, and biological fate. Depending on the type of DNA lesion produced (e.g., interference with DNA replication or RNA transcription), the organ or cell type inflicted (e.g., cell cycle or differentiation status, metabolic state, activity of clearance and detoxification mechanisms, the cellular condition or micro-environment), and the degree of exposure, outcomes of cancer treatment can largely differ. These considerations provide a conceptual framework in which different classes of chemotherapeutics contribute to the development of toxicities and accelerated aging of different organ systems. Here, we summarize frequently observed side-effects in (pediatric) ex-cancer patients and discuss which types of DNA damage might be responsible.
Author Vermeij, Wilbert P
van den Boogaard, Winnie M C
Komninos, Daphne S J
AuthorAffiliation 1 Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands; w.vandenboogaard@prinsesmaximacentrum.nl (W.M.C.v.d.B.); d.s.j.komninos@prinsesmaximacentrum.nl (D.S.J.K.)
2 Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, The Netherlands
AuthorAffiliation_xml – name: 1 Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands; w.vandenboogaard@prinsesmaximacentrum.nl (W.M.C.v.d.B.); d.s.j.komninos@prinsesmaximacentrum.nl (D.S.J.K.)
– name: 2 Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, The Netherlands
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  orcidid: 0000-0001-5712-3990
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35158895$$D View this record in MEDLINE/PubMed
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Issue 3
Keywords cancer treatment
cancer survivors
chemotherapy
premature aging
DNA damage
Language English
License Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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content type line 23
These authors contributed equally to this work.
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SecondaryResourceType review_article
Snippet Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy....
Simple SummaryThe number of children and adults with cancer that are completely cured is still increasing thanks to effective anti-cancer therapy, but they may...
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StartPage 627
SubjectTerms 20th century
Aging
Antibiotics
Apoptosis
Cancer
Cancer therapies
Cell cycle
Cell differentiation
Cell division
Chemotherapy
Children
Creatinine
Deoxyribonucleic acid
Detoxification
DNA
DNA biosynthesis
DNA damage
DNA repair
Drug dosages
Genomes
Genomic instability
Genotoxicity
Kidneys
Leukemia
Liver
Lymphoma
Patients
Pediatrics
Quality of life
Radiation therapy
Review
Sarcoma
Side effects
Toxicity
Transcription
Tumors
Urine
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Title Chemotherapy Side-Effects: Not All DNA Damage Is Equal
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Volume 14
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