Cited by 1,189DNA Repair MechanismsCell death mechanisms and regulationCancer-related Molecular Pathways

DNA damage and the balance between survival and death in cancer biology

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Roos, Wynand P., Thomas, Adam D., Kaina, Bernd·2016·Nature Reviews Cancer

Abstract

DNA is vulnerable to damage resulting from endogenous metabolites, environmental and dietary carcinogens, some anti-inflammatory drugs, and genotoxic cancer therapeutics. Cells respond to DNA damage by activating complex signalling networks that decide cell fate, promoting not only DNA repair and survival but also cell death. The decision between cell survival and death following DNA damage rests on factors that are involved in DNA damage recognition, and DNA repair and damage tolerance, as well as on factors involved in the activation of apoptosis, necrosis, autophagy and senescence. The pathways that dictate cell fate are entwined and have key roles in cancer initiation and progression. Furthermore, they determine the outcome of cancer therapy with genotoxic drugs. Understanding the molecular basis of these pathways is important not only for gaining insight into carcinogenesis, but also in promoting successful cancer therapy. In this Review, we describe key decision-making nodes in the complex interplay between cell survival and death following DNA damage.

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Crossref · 10.1038/nrc.2015.2

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  • Intrinsic apoptosis is initiated by microenvironmental perturbations including growth factor withdrawal, DNA damage, ER stress, ROS overload, replication stress, microtubular alterations or mitotic defects.

    “Intrinsic apoptosis is a form of RCD initiated by a variety of microenvironmental perturbations including (but not limited to) growth factor withdrawal, DNA damage, endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) overload, replication stress, microtubular alterations or mitotic defects [29–34].”

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Authors
Roos, W. P., Thomas, A. D., & Kaina, B.
Affiliations
University Medical Center of the Johannes Gutenberg University Mainz (DE)
Corresponding author
Kaina, Bernd
Venue
Nature Reviews Cancer
Published
2015-12-18
Volume
16
Issue
1
Pages
20-33
ISSN
  • 1474-175X (ISSN-L)
  • 1474-1768
OpenAlex
W2212776653
Cited by
1,189
References
199
Citations by year
2026: 67 · 2025: 97 · 2024: 107 · 2023: 123 · 2022: 141 · 2021: 156 · 2020: 133 · 2019: 112 · 2018: 103 · 2017: 95 · 2016: 50 · 2015: 4
FWCI
8.17
Type
journal article
Language
en
Open access
Locations
  • Nature reviews. Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • UWE Research Repository (UWE Bristol) (submittedVersion, cc-by)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
DNA damage response, cell fate, DNA repair, apoptosis, necrosis, autophagy, cellular senescence, carcinogenesis, DNA damage recognition, damage tolerance, cell survival
MeSH terms
Cell Survival, DNA Damage, DNA Repair, Humans, Neoplasms, Cell Death

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