The future perspective of PARP inhibitors
Abstract - 1818 PDF - 516Abstract
The protein poly (ADP-ribose) polymerase (PARP) plays an important role in DNA base excision repair and repair of DNA single-strand breaks[1] and might also be involved in DNA double-strand break repair[2]. For tumor cells with homologous recombination deficiency (HRD), such as ovarian cancer cells with BRCA1/2 mutations, interfering with PARP activity leads to unrepaired single-strand DNA breaks and subsequent formation of double- strand breaks. This results in synthetic lethality of cancer cells with HRD. In 2005, the antitumor effect of inhibiting the PARP enzyme in BRCA1/2-mutated cancer cells was first demonstrated in preclinical tumor xenografts[3,4]. After a decade of developing drugs targeting PARP for clinical use in patients with BRCA- mutated cancer, in recent years several PARP inhibitors have finally been approved by the U.S. Food and Drug Administration for the treatment of ovarian cancer.
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DOI: http://dx.doi.org/10.18282/amor.v3.i6.256
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