Nan Li 1 , Yifan Wang 1,2 , Weiye Deng 3 , Steven H Lin 1,3 Show Affiliations »
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities: Chemical
Disease
Gene
Keywords:
BRCA mutation; PARP inhibitors; Tankyrase inhibitors; ovarian cancers; poly-ADP-ribose polymerase 1; synthetic lethal.
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Year: 2019
PMID： 30417796 DOI： 10.2174/1871520618666181109164645
Source DB: PubMed Journal: Anticancer Agents Med Chem ISSN： 1871-5206 Impact factor: 2.505