Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer

Abstract

Rucaparib camsylate (CO-338, AG-014699, PF-01367338) is a potent PARP-1, PARP-2, and PARP-3 inhibitor. Phase I and II studies demonstrated clinical efficacy in both BRCA-mutated (inclusive of germline and somatic) ovarian tumors and ovarian tumors with homologous recombination deficiency (HRD) loss of heterozygosity (LOH). Rucaparib has received the US Food and Drug Administration (FDA) approval for patients with deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer who have been treated with two or more chemotherapies. There is evidence to suggest that rucaparib has clinical efficacy against ovarian tumors with high HRD-LOH. Rucaparib’s companion diagnostic FoundationFocus™ CDxBRCA test is the first FDA-approved next-generation sequencing-based companion diagnostic test designed to identify patients likely to respond to rucaparib. This article reviews the mechanisms of action, safety, approval, and indications for use of the PARP inhibitor rucaparib as well as future trials and use of rucaparib’s companion diagnostic test.

Retracted: Inositol polyphosphate‐4‐phosphatase type II and rucaparib treatment inhibit the growth of osteosarcoma cells dependent on phosphoinositide 3‐kinase/protein kinase B pathway

“…[21][22][23] Additionally, Yuen et al 24 reported that the expression of INPP4B was declined in nasopharyngeal cancer cells. 26 In vitro studies revealed that rucaparib induced cytotoxicity might relate to the inhibition of PARP enzyme activity and increase the formation of PARP-DNA complexes, thereby leading to DNA damage and cell apoptosis. 25 These studies apparently explained that the expression level of INPP4B was negatively correlated F I G U R E 5 Effect of rucaparib on cell proliferation and apoptosis in both SaOS2 and U2OS cells.…”

“…Rucaparib is one of the PARP inhibitor, which is successfully obtained a license by the Food and Drug Administration and indicated as a new drug for the treatment of patients with advanced ovarian cancer. 26 In vitro studies revealed that rucaparib induced cytotoxicity might relate to the inhibition of PARP enzyme activity and increase the formation of PARP-DNA complexes, thereby leading to DNA damage and cell apoptosis. 27,28 In vivo experiments demonstrated that rucaparib could suppress tumor growth in glioblastoma and small cell lung cancer.…”

PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs

“…Other adaptation diseases also include breast carcinoma, melanoma, and unspecified solid tumors [ 77 ]. Rucaparib (AG-014669, PF-01367338, trade name: Rubraca, given orally), an FDA granted and recently approved PARP1-based drug for BRCA-mutant ovarian carcinoma patients, is indicated for therapy one line earlier than olaparib [ 78 ]. It has also been investigated against breast, pancreatic, fallopian tube, and peritoneal carcinomas [ 79 ].…”

“…It has also been investigated against breast, pancreatic, fallopian tube, and peritoneal carcinomas [ 79 ]. Further investigations have significantly found the tumoricidal effect of rucaparib in human non-BRCA-mutant ovarian cancer for both monotherapy and combination therapy [ 78 , 80 ]. Veliparib (ABT-888), a benzimidazole-4-carboxamide derivative, has been preclinically studied against breast, ovarian, lung, pancreatic, prostate, testicular and colorectal cancers, and other unspecified solid tumors.…”

Management of QT prolongation induced by anti-cancer drugs: Target therapy and old agents. Different algorithms for different drugs

“…Rucaparib was the first approved PARP inhibitor used in the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer that have been treated with two or more chemotherapies (Study 42, Clini-calTrials.gov NCT01078662) [67,68]. The safety of rucaparib was evaluated in 377 patients with advanced ovarian cancer [69].…”