Advances and perspectives of PARP inhibitors
Open accessAbstract
DNA damage repair deficiency leads to the increased risk of genome instability and oncogenic transformation. In the meanwhile, this deficiency could be exploited for cancer treatment by inducing excessive genome instability and catastrophic DNA damage. Continuous DNA replication in cancer cells leads to higher demand of DNA repair components. Due to the oncogenic loss of some DNA repair effectors (e.g. BRCA) and incomplete DNA repair repertoire, some cancer cells are addicted to certain DNA repair pathways such as Poly (ADP-ribose) polymerase (PARP)-related single-strand break repair pathway. The interaction between BRCA and PARP is a form of synthetic lethal effect which means the simultaneously functional loss of two genes lead to cell death, while defect in any single gene has a slight effect on cell viability. Based on synthetic lethal theory, Poly (ADP-ribose) polymerase inhibitor (PARPi) was developed aiming to selectively target cancer cells harboring BRCA1/2 mutations. Recently, a growing body of evidence indicated that a broader population of patients could benefit from PARPi therapy far beyond those with germline BRCA1/2 mutated tumors. Numerous biomarkers including homologous recombination deficiency and high level of replication pressure also herald high sensitivity to PARPi treatment. Besides, a series of studies indicated that PARPi-involved combination therapy such as PARPi with additional chemotherapy therapy, immune checkpoint inhibitor, as well as targeted agent had a great advantage in overcoming PARPi resistance and enhancing PARPi efficacy. In this review, we summarized the advances of PARPi in clinical application. Besides, we highlighted multiple promising PARPi-based combination strategies in preclinical and clinical studies.
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PARP is an ideal target for drug development as the core of SSB repair.
“As the core of SSB repair, PARP is the ideal target for drug development [222].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [222]
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- Authors
- Yi, M., Dong, B., Qin, S., Chu, Q., Wu, K., & Luo, S.
- Affiliations
- Tongji Hospital (CN)
- Zhengzhou University (CN)
- Corresponding author
- Wu, Kongming
- Luo, Suxia
- Venue
- Experimental Hematology & Oncology
- Published
- 2019-11-11
- Volume
- 8
- Issue
- 1
- Pages
- 29-29
- ISSN
- 2162-3619 (ISSN-L)
- PMC
- PMC6849303
- OpenAlex
- W2987653633
- Cited by
- 117
- References
- 104
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 7 · 2023: 18 · 2022: 19 · 2021: 33 · 2020: 22
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Experimental Hematology and Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81874120, 81572608, 81672984)
- Wuhan Municipal Science and Technology Bureau (2017060201010170)
- Natural Science Foundation of Henan Province (162300410266)
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- PARP inhibitors, DNA repair deficiency, synthetic lethality, BRCA mutations, homologous recombination deficiency, single-strand break repair, genomic instability, PARP inhibitor resistance, combination therapy, immune checkpoint inhibitors, combination chemotherapy
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