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Comment
. 2011 Feb 15;19(2):165-7.
doi: 10.1016/j.ccr.2011.01.047.

PARP inhibitors in cancer therapy: promise, progress, and puzzles

Leif W Ellisen  1
Affiliations
Comment

PARP inhibitors in cancer therapy: promise, progress, and puzzles

Leif W Ellisen. Cancer Cell. .

Abstract

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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Figures

Figure 1
Figure 1. PARP inhibitor treatment of BRCA1/2-associated and sporadic cancers
Normal cells have intact base excision repair and homologous recombination that are mediated by PARP and BRCA1/2-dependent pathways, respectively. In germline BRCA1 or BRCA2 mutations carriers, the capacity for HR is often lost during tumorigenesis due to the inactivation of the remaining wild type allele. PARP inhibitor treatment disables repair of spontaneous DNA damage in these tumor cells, leading to their death. Sporadic tumors including triple-negative breast cancer may have defects in BRCA1/2 expression and/or function. Treatment combining a PARP inhibitor with DNA-damaging chemotherapy may be an effective strategy for some of these tumors.
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References

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