Advances in using PARP inhibitors to treat cancer

BMC Medicine

Minireview

Robert J Kinders¹  Ralph E Parchment¹  Jay Ji¹  Joseph E Tomaszewski²  Alice Chen²  Shivaani Kummar²  James H Doroshow³ 

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

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

DOI  :  10.1186/1741-7015-10-25

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

来源: Springer

【 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】

Unknown   
© Kummar et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.