Journal
BMC MEDICINE
Volume 10, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/1741-7015-10-25
Keywords
synthetic lethality; DNA repair; PARP clinical trials
Categories
Funding
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- NIH, National Cancer Institute, Center for Cancer Research
- Division of Cancer Treatment and Diagnosis of the National Cancer Institute
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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.
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