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Updated: Dec 5, 2025
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
The DNA damaging revolution
Bulent Cetin1, Chiara A Wabl2, Ozge Gumusay2
1Department of Internal Medicine, Division of Medical Oncology, Suleyman Demirel University, Faculty of Medicine, Isparta, Turkey.
Abstract:
Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that plays a critical role in the repair of single-strand DNA damage via the base excision repair pathway. PARP inhibitors have substantial single-agent antitumor activity by inducing synthetic lethality. They have also emerged as promising anticancer targeted therapies, especially in tumors harboring deleterious germline or somatic breast cancer susceptibility gene (BRCA) mutations. PARP inhibition produces single-strand DNA breaks, which may be repaired by homologous recombination, a process partially dependent on BRCA1 and BRCA2. The PARP inhibitors olaparib, veliparib, talazoparib, niraparib, and rucaparib have predominantly been studied in patients with breast or ovarian cancers associated with deleterious germline mutations in BRCA1 and BRCA2. Ongoing clinical trials are evaluating the role of PARP inhibitors alone and in combination with other therapies, including selective inhibitors against key targets involved in the DNA damage response. In this review we summarize the use of PARP inhibitors in various tumor types, as well as possible approaches for overcoming resistance to PARP inhibitors.
Insights
Poly(ADP-ribose) polymerase (PARP) inhibitors show significant antitumor effects by creating synthetic lethality, particularly in BRCA-mutated cancers. Research is exploring their use across various tumor types and strategies to overcome treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Poly(ADP-ribose) polymerase (PARP) is a key enzyme in DNA repair pathways.
- PARP inhibitors induce synthetic lethality, showing antitumor activity, especially in BRCA-mutated cancers.
- PARP inhibitors like olaparib, veliparib, talazoparib, niraparib, and rucaparib are studied in breast and ovarian cancers.
Purpose of the Study:
- To review the application of PARP inhibitors in diverse tumor types.
- To explore strategies for overcoming resistance to PARP inhibitors.
- To summarize ongoing clinical trials evaluating PARP inhibitors alone and in combination therapies.
Main Methods:
- Literature review of PARP inhibitors in cancer therapy.
- Analysis of clinical trial data for PARP inhibitors.
- Summary of DNA damage response pathways and resistance mechanisms.
Main Results:
- PARP inhibitors demonstrate significant single-agent antitumor activity.
- Efficacy is pronounced in tumors with BRCA1/BRCA2 mutations.
- Ongoing trials investigate combinations with other targeted therapies.
Conclusions:
- PARP inhibitors are promising targeted therapies for specific cancer types.
- Further research is needed to broaden their application and manage resistance.
- Combination strategies hold potential for enhanced therapeutic outcomes.
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