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Updated: May 2, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
DNA repair in cancer: emerging targets for personalized therapy
Rachel Abbotts1, Nicola Thompson1, Srinivasan Madhusudan1
1University of Nottingham, Academic Unit of Oncology, Division of Oncology, School of Medicine, Nottingham University Hospitals, City Hospital Campus, Nottingham, UK.
Abstract:
Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer.
Insights
DNA repair is crucial for maintaining genomic integrity and preventing cancer. Targeting DNA repair pathways, particularly through synthetic lethality, offers a promising strategy for personalized cancer therapy by exploiting vulnerabilities in cancer cells.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Genomic deoxyribonucleic acid (DNA) faces constant damage from internal and external sources.
- Mammalian cells possess DNA repair mechanisms to preserve genomic integrity.
- Defective DNA repair contributes to cancer development and aggressive tumor behavior.
Purpose of the Study:
- To review recent advancements in targeting DNA repair for cancer therapy.
- To highlight the potential of synthetic lethality in cancer treatment strategies.
Main Methods:
- Review of current scientific literature on DNA repair mechanisms.
- Analysis of synthetic lethality approaches in preclinical and clinical cancer research.
Main Results:
- Overexpression of DNA repair factors has prognostic and predictive value in cancer patients.
- DNA repair inhibition is an emerging and effective anticancer therapeutic strategy.
- Synthetic lethality targeting DNA repair presents a promising avenue for personalized cancer medicine.
Conclusions:
- Targeting DNA repair, especially via synthetic lethality, is a key strategy in modern oncology.
- Understanding DNA repair dynamics is crucial for developing effective cancer treatments.
- Synthetic lethality offers a targeted approach to exploit cancer-specific vulnerabilities.
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