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The role of PARP1 in the DNA damage response and its application in tumor therapy
Zhifeng Wang, Fengli Wang, Tieshan Tang, Caixia Guo
Frontiers of Medicine 2012, Volume 6, Issue 2, Pages 156-164 doi: 10.1007/s11684-012-0197-3
Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.
Keywords： PARP1 synthetic lethality PARP inhibitor DNA repair cancer NHEJ
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