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Published on: September 1, 2019
DNA damage and the balance between survival and death in cancer biology
Wynand P Roos1, Adam D Thomas1, Bernd Kaina1
1Institute of Toxicology, University Medical Center, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany.
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.
Insights
Cells activate complex signaling networks to manage DNA damage, deciding between survival and death. Understanding these pathways is crucial for cancer therapy and understanding carcinogenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DNA damage is a constant threat from various sources, including metabolites, carcinogens, and therapies.
- Cellular responses to DNA damage involve intricate signaling networks that govern cell fate.
- These pathways are critical in both cancer development and the effectiveness of cancer treatments.
Purpose of the Study:
- To review the key decision-making nodes in cellular responses to DNA damage.
- To elucidate the interplay between cell survival and cell death pathways.
- To highlight the significance of these pathways in cancer initiation, progression, and therapy.
Main Methods:
- Literature review of molecular mechanisms.
- Analysis of signaling networks involved in DNA damage response.
- Synthesis of information on cell fate determination pathways.
Main Results:
- DNA damage triggers complex signaling networks that dictate cell fate.
- Key decision-making nodes control the balance between DNA repair, survival, and various forms of cell death (apoptosis, necrosis, autophagy, senescence).
- These intertwined pathways are fundamental to cancer biology and therapeutic outcomes.
Conclusions:
- Understanding the molecular basis of DNA damage response pathways is essential for advancing cancer research and treatment.
- Targeting these pathways holds promise for improving cancer therapy efficacy.
- The review provides insights into the critical interplay governing cell survival and death following DNA damage.
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