کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6190097 1257269 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
De la découverte du poly(ADP-ribose) aux inhibiteurs PARP en thérapie du cancer
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی تومور شناسی
پیش نمایش صفحه اول مقاله
De la découverte du poly(ADP-ribose) aux inhibiteurs PARP en thérapie du cancer
چکیده انگلیسی
Poly(ADP-ribosyl)ation is a post-translational modification catalyzed by poly(ADP-ribose) polymerases. PARP-1 is a molecular sensor of DNA breaks, playing a key role in the spatial and temporal organization of their repair, contributing to the maintenance of genome integrity and cell survival. The fact that PARP inhibition impairs efficacy of break repair has been exploited as anticancer strategies to potentiate the cytotoxicity of anticancer drugs and radiotherapy. Numerous clinical trials based on this innovative approach are in progress. PARP inhibition has also proved to be exquisitely efficient to kill tumour cells deficient in double strand break repair by homologous recombination, such as cells mutated for the breast cancer early onset genes BRCA1 or BRCA2, by synthetic lethality. Several phase III clinical trials are in progress for the treatment of breast and ovarian cancers with BRCA mutations and the PARP inhibitor olaparib has just been approved for advanced ovarian cancers with germline BRCA mutation. This review recapitulates the history from the discovery of poly(ADP-ribosyl)ation reaction to the promising therapeutic applications of its inhibition in innovating anticancer strategies. Benefits, hopes and obstacles are discussed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bulletin du Cancer - Volume 102, Issue 10, October 2015, Pages 863-873
نویسندگان
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