Poly (ADP-Ribose) Polymerases (PARPs) and PARP Inhibitor-Targeted Therapeutics

Author(s): Nan Li*, Yifan Wang, Weiye Deng, Steven H. Lin*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 19 , Issue 2 , 2019

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Graphical Abstract:


Background: Poly-ADP-ribosylation, that is, adding ADP-ribose moieties to a protein, is a unique type of protein post-translational modification that regulates various cellular processes such as DNA repair, mitosis, transcription, and cell growth. Small-molecule inhibitors of poly-ADP-ribose polymerase 1 (PARP1) have been developed as anticancer agents because inhibition of PARP enzymes may be a synthetic lethal strategy for cancers with or BRCA2 mutations. However, there are still questions surrounding PARP inhibitors.

Methods/Results: Data were collected from Pubmed, Medline, through searching of these keywords: “PARP”, “BRCA”, “Synthetic lethal” and “Tankyrase inhibitors”. We describe the current knowledge of PARP inhibition and its effects on DNA damage; mechanisms of resistance to PARP inhibitors; the evolution of PARP inhibitors; and the potential use of PARP5a/b (tankyrases) inhibitors in cancer treatment.

Conclusion: PARP inhibitors are already showing promise as therapeutic tools, especially in the management of BRCA-mutated breast and ovarian cancers but also in tumors with dysfunctional BRCA genes. Small-molecule tankyrase inhibitors are important for increasing our understanding of tankyrase biology.

Keywords: PARP inhibitors, BRCA mutation, synthetic lethal, Tankyrase inhibitors, poly-ADP-ribose polymerase 1, ovarian cancers.

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Year: 2019
Page: [206 - 212]
Pages: 7
DOI: 10.2174/1871520618666181109164645
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