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Updated: May 20, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Base excision repair: contribution to tumorigenesis and target in anticancer treatment paradigms
1Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Abstract:
Cancer treatments often lose their effectiveness due to the development of multiple drug resistance. Thus, identification of key proteins involved in the tumorigenic process and the survival mechanism(s), coupled with the design of novel therapeutic compounds (such as small molecule inhibitors), are essential steps towards the establishment of improved anticancer treatment strategies. DNA repair pathways and their proteins have been exposed as potential targets for combinatorial anticancer therapies that involve DNA-interactive cytotoxins, such as alkylating agents, because of their central role in providing resistance against DNA damage. In addition, an understanding of the tumor-specific genetics and associated DNA repair capacity has allowed research scientists and clinicians to begin to devise more targeted treatment strategies based on the concept of synthetic lethality. In this review, the repair mechanisms, as well as the links to cancer progression and treatment, of three key proteins that function in the base excision repair pathway, i.e. APE1, POLβ, and FEN1, are discussed.
Insights
This review explores DNA repair proteins, including AP Endonuclease 1 (APE1), DNA Polymerase beta (POLβ), and Flap Endonuclease 1 (FEN1), as targets for novel cancer therapies to overcome drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer treatments face challenges due to multi-drug resistance.
- DNA repair pathways are crucial for cancer cell survival and treatment resistance.
- Targeting DNA repair offers a strategy for improved anticancer therapies.
Purpose of the Study:
- To review the roles of APE1, POLβ, and FEN1 in DNA repair.
- To discuss the link between these proteins, cancer progression, and treatment resistance.
- To highlight their potential as targets for novel therapeutic strategies.
Main Methods:
- Literature review of DNA repair mechanisms.
- Analysis of the base excision repair pathway.
- Examination of protein functions in cancer progression and drug resistance.
Main Results:
- APE1, POLβ, and FEN1 are key proteins in base excision repair.
- Their functions are linked to cancer development and resistance to therapy.
- Understanding these proteins aids in developing targeted treatments.
Conclusions:
- Targeting APE1, POLβ, and FEN1 presents a promising avenue for overcoming cancer drug resistance.
- Combinatorial therapies involving DNA-interactive agents and DNA repair inhibitors warrant further investigation.
- Synthetic lethality approaches targeting DNA repair offer personalized treatment strategies.
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