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Advances in using PARP inhibitors to treat cancer

Shivaani Kummar1, Alice Chen1, Ralph E Parchment2, Robert J Kinders2, Jay Ji2, Joseph E Tomaszewski1 and James H Doroshow13*

Author affiliations

1 Division of Cancer Treatment and Diagnosis, Bldg. 31, Room 3A-44, 31 Center Drive, National Cancer Institute, Bethesda, MD, 20892, USA

2 Applied/Developmental Research Directorate, Science Applications International Corporation-Frederick, Inc., Bldg. 431, 1050 Boyles St., National Cancer Institute at Frederick, Frederick, MD, 21702 USA

3 Center for Cancer Research, Bldg. 37, Room 1052, 37 Convent Drive, National Cancer Institute, Bethesda, MD, 20892 USA

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Citation and License

BMC Medicine 2012, 10:25  doi:10.1186/1741-7015-10-25

Published: 9 March 2012

Abstract

The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.

Keywords:
synthetic lethality; DNA repair; PARP clinical trials