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      Targeted treatment of advanced ovarian cancer: spotlight on rucaparib

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          Abstract

          The last 2 years have ushered in a new era in ovarian cancer therapy with the US Food and Drug Administration’s (FDA) approval of poly-ADP ribose polymerase (PARP) inhibitors (PARPi). One of the deadliest cancers that women experience, ovarian cancer, is most often diagnosed in advanced stages. Although cytoreductive surgery and (platinum/taxane-based) chemotherapy can place the majority of patients into remission, most will experience a relapse of their disease in their lifetime. This has led to studies exploring the benefits and efficacy of maintenance treatment. This review will briefly discuss the history of maintenance therapy as well as focus on the FDA’s approval of rucaparib and its companion tumor profiling test, in the US. It will describe how women with deleterious mutations in the BRCA gene, through their inherent deficiency in homologous recombination, presented scientists with a target to exploit through a concept known as synthetic lethality. Not only did this lead to a targeted treatment for BRCA mutation carriers but for other patients with deficiencies in homologous recombination and, more broadly, also in platinum-sensitive patients. The focus of this review will be on rucaparib in the US, approved for both maintenance of platinum-sensitive recurrent ovarian cancer and treatment in the third-line setting and beyond. It has the broadest indication amongst the three PARPi in ovarian cancer. Furthermore, the ongoing trials using rucaparib in ovarian cancer and other disease types will be discussed.

          Most cited references27

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          Linkage of early-onset familial breast cancer to chromosome 17q21.

          Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region.
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            ACOG Practice Bulletin No. 106: Intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles.

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              A mechanism for gene conversion in fungi

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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2018
                02 November 2018
                : 14
                : 2189-2201
                Affiliations
                Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of California, Irvine Medical Center, Orange, CA, USA, ktewari@ 123456uci.edu
                Author notes
                Correspondence: Krishnansu S Tewari, Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of California, Irvine Medical Center, 333 The City Boulevard West, Orange, CA 92868, USA, Tel +1 714 456 8020, Fax +1 714 456 6632, Email ktewari@ 123456uci.edu
                Article
                tcrm-14-2189
                10.2147/TCRM.S149248
                6223341
                00708550-c25a-4501-90d1-cedea8f69277
                © 2018 Pearre and Tewari. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Medicine
                brca,parp inhibitor,targeted therapy,rucaparib,ovarian cancer
                Medicine
                brca, parp inhibitor, targeted therapy, rucaparib, ovarian cancer

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