Advances in using PARP inhibitors to treat cancer

BMC Medicine

James H Doroshow²  Joseph E Tomaszewski¹  Jay Ji³  Robert J Kinders³  Ralph E Parchment³  Alice Chen¹  Shivaani Kummar¹ 

[1] Division of Cancer Treatment and Diagnosis, Bldg. 31, Room 3A-44, 31 Center Drive, National Cancer Institute, Bethesda, MD, 20892, USA;Center for Cancer Research, Bldg. 37, Room 1052, 37 Convent Drive, National Cancer Institute, Bethesda, MD, 20892 USA;Applied/Developmental Research Directorate, Science Applications International Corporation-Frederick, Inc., Bldg. 431, 1050 Boyles St., National Cancer Institute at Frederick, Frederick, MD, 21702 USA

关键词: PARP clinical trials;    DNA repair;    synthetic lethality;   

Others  :  1126328
DOI  :  10.1186/1741-7015-10-25

 received in 2011-11-02, accepted in 2012-03-09,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Kummar et al; licensee BioMed Central Ltd.

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