کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5534958 1551360 2017 41 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Poly(ADP-ribose) polymerase activity and inhibition in cancer
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Poly(ADP-ribose) polymerase activity and inhibition in cancer
چکیده انگلیسی
Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination. Five PARP inhibitors are now in late-stage development in clinical trials that are seeking to expand the understanding of targeted therapies and DNA repair defects in human cancer. This review examines the cell biology of PARP, the discovery of synthetic lethality with HR deficiency, the clinical development of PARP inhibitors, and the role of PARP inhibitors in ongoing clinical trials and clinical practice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Seminars in Cell & Developmental Biology - Volume 63, March 2017, Pages 144-153
نویسندگان
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