PARP Inhibitors in Cancer Therapy: Promise, Progress, and Puzzles

Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Cancer cell (Impact Factor: 23.52). 02/2011; 19(2):165-7. DOI: 10.1016/j.ccr.2011.01.047
Source: PubMed


A recent article in the New England Journal of Medicine by O'Shaughnessy et al. provides evidence that a treatment strategy aimed at inducing DNA damage with chemotherapy while simultaneously disabling repair using a PARP inhibitor might offer hope for patients with a treatment-refractory form of breast cancer.

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Available from: Leif W Ellisen, May 18, 2015
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    • "Here, poly (ADP-ribose) polymerase (PARP) inhibitor sensitization of cells to MMS-induced killing is dependent on the presence of the 5′-dRP group [27]. The topic is timely as PARP inhibitors are currently being evaluated in cancer chemotherapy [28]. Although the budding yeast system does not contain the PARP enzyme, this system can nonetheless informs us about the metabolism of the 5′-dRP group in BER intermediates. "
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    • "The prototype of these drugs are inhibitors of poly ADP(ribose) polymerase (PARP), enzymes required for single-strand break and base-excision repair [36]. Combinations of PARP inhibitors with DNA damaging chemotherapy are already showing early promise in the treatment of TNBC [37, 38]. Activation of TAp73 may be involved in the response to unrepaired DNA damage in at least a subset of these tumors. "
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