TY - JOUR
T1 - Poly (ADP-ribose) polymerases (PARPs) and PARP inhibitor-targeted therapeutics
AU - Li, Nan
AU - Wang, Yifan
AU - Deng, Weiye
AU - Lin, Steven H.
N1 - Funding Information:
This work is supported by the Mabuchi Program in Targeted Radiotherapy, Cancer Center Support (Core) rGant AC016672 rofm the National Cancer Institute, National Institutes of Health, to the University of Texas MD Anderson Cancer Center. The authors thank Christine Wogan of Division of Radiation Oncology, MD Anderson Cancer Center for editorial assistance.
Publisher Copyright:
© 2019 Bentham Science Publishers.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - BRCA mutation
KW - Ovarian cancers
KW - PARP inhibitors
KW - Poly-ADP-ribose polymerase 1
KW - Synthetic lethal
KW - Tankyrase inhibitors
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U2 - 10.2174/1871520618666181109164645
DO - 10.2174/1871520618666181109164645
M3 - Review article
C2 - 30417796
AN - SCOPUS:85069486411
SN - 1871-5206
VL - 19
SP - 206
EP - 212
JO - Anti-cancer agents in medicinal chemistry
JF - Anti-cancer agents in medicinal chemistry
IS - 2
ER -