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Curr Breast Cancer Rep (2010) 2:1–3 DOI 10.1007/s12609-010-0001-9 CLINICAL TRIAL REPORT Exploring the Concept of Synthetic Lethality to Improve Therapeutic Options for Patients with Breast Cancer Conleth G. Murphy & Maura N. Dickler Published online: 21 February 2010 Springer Science+Business Media, LLC 2010 Fong PC, Boss DS, Yap TA et al.: Inhibition of poly(ADP- (particularly those of the breast and ovary, although an Ribose) polymerase in tumors from BRCA mutation increased risk of other tumors has been described) [3]. carriers. N Engl J Med 2009, 361:123–128. Tumors in germline mutation carriers arise when the remaining normal allele is lost (loss of heterozygosity) or silenced by epigenetic changes. Rating Poly(ADP-ribose) polymerase 1 (PARP1) is a protein that is of key importance in the base excision repair (BER) Of major importance pathway, where it is involved in the signalling and recruitment of repair proteins to DNA single-strand breaks. The use of inhibitors of PARP1 as a therapeutic strategy in Introduction tumors of BRCA mutation carriers is based on the concept of synthetic lethality, a lethal synergy between two DNA damage is a frequent event in cells and may arise individually nonlethal events [4]. Inhibiting PARP1 is from endogenous stresses such
Current Breast Cancer Reports – Springer Journals
Published: Feb 21, 2010
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