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

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

Anticancer Agents Med Chem. 2018 Nov 09;:

Authors: Li N, Wang Y, Deng W, Lin SH

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 BRCA1 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 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.

PMID: 30417796 [PubMed - as supplied by publisher]

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