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Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor used to treat recurrent ovarian and prostate cancers in previously treated adults.
Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor used to treat recurrent ovarian and prostate cancers in previously treated adults.
PARPs play a role in DNA repair by activating DNA damage response pathways, such as base excision repair, and facilitating DNA repair. PARPs were evaluated as novel anticancer therapeutic targets after discovering that PARP-1 inhibitors reduce tumour growth in BRCA-deficient cancers. BRCA1 and BRCA2 are tumour suppressor genes involved in various cellular processes related to cell growth and death, including DNA repair. More specifically, BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair. Cancer cells with a deleterious BRCA mutation are HR-deficient, resulting in unregulated and aberrant cell repair and growth. Rucaparib inhibits PARP1, PARP2, and PARP3. Inhibiting PARP traps the enzyme on damaged DNA, halting the repair process and forming toxic PARP–DNA complexes. Alternatively, other DNA repair processes such as error-prone nonhomologous end joining (NHEJ) or alternative end-joining pathways can be initiated, leading to mutations or chromosomal change. Further DNA damage can trigger cancer cell apoptosis and cell death. Typically, inhibition of PARP converts single-strand breaks in DNA to double-strand breaks at replication forks. HR DNA repair pathways repair double-strand breaks; however, HR-deficient cancer cells lack this repair mechanism. Because HR-deficient cancer cells are more vulnerable to unsalvageable DNA damage, rucaparib-induced PARP inhibition leads to synthetic lethality. In this phenomenon, two non-lethal defects (HR deficiency and PARP inhibition) combine and cause cell death.
Rucaparib is indicated for the maintenance treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)- associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Under accelerated approval by the FDA, rucaparib is also indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.
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One entry per invention. Patent families filed in the US, EP, WO and CN offices.
