Abstract
The nuclear enzyme poly (ADP-ribose) polymerase (PARP) represents an important novel target in the treatment of ovarian cancer. This article charts over 50 years of research from the discovery of the first PARP enzyme in 1963, to the approval and licensing in 2015 of the first PARP inhibitor, olaparib (Lynparza), in the treatment of BRCA-mutated ovarian cancer.
Highlights
Walsh C, Li AJ, Leuchter R, Gordon O, Garcia-Closas M, Gayther SA, Chanock SJ, Antoniou AC, Pharoah PD; EMBRACE; kConFab Investigators; Cancer Genome Atlas Research Network (2012) Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer
Work by Anthony Chalmers’ group has shown that this radio-potentiation is enhanced in rapidly proliferating cells and cells defective in DNA DSB repair compared with normal tissue (Loser et al, 2010)
These data support a role for combining radiotherapy and PARP inhibitors in patients with cancer, and clinical trials are underway with results eagerly awaited
Summary
Sythesis-dependent Second-end capture double strand annealing holliday–junction formation. Binds to the exposed DNA, and this binding enables the loading of Rad onto the break and the formation of the presynaptic filament (Yang et al, 2002). Given the functions of BRCA1 and 2, it would be logical to hypothesise that deficiencies within either gene will result in defective HRR and subsequent loss of efficient and effective DNA DSB repair
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