The Medical Letter on Drugs and Therapeutics
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1535
PARP Inhibitors for Ovarian Cancer
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Three oral poly(ADP-ribose) polymerase (PARP) inhibitors have been approved by the FDA for treatment of advanced, recurrent ovarian cancer. Olaparib (Lynparza – AstraZeneca), niraparib (Zejula – Tesaro), and rucaparib (Rubraca – Clovis) are each approved for somewhat different indications and for patients with different biomarkers (see Table 2).

MECHANISM OF ACTION — PARPs are involved in many cellular functions, including DNA transcription and repair of single-strand breaks. PARP inhibition leads to double-strand DNA breaks that activate homologous recombination (HR) repair, but when HR is defective, as it is in patients with BRCA mutations, an error-prone repair mechanism is activated that is unable to accurately repair these breaks, leading to DNA damage, apoptosis, and cell death (synthetic lethality). PARP inhibitors are cytotoxic for cancer ... more      

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Title: PARP Inhibitors for Ovarian Cancer
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