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    Overview of fuzuloparib in the treatment of ovarian cancer: background and future perspective

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    https://www.riss.kr/link?id=A108622465

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    다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

    Over the last decade, clinical trials using various poly ADP ribose polymerase (PARP) inhibitors on patients with ovarian cancer have shown promising results. The introduction of PARP inhibitors has changed the treatment landscape and improved outcomes for patients with ovarian cancer. Fuzuloparib, developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd., is a novel orally available small molecule PARP inhibitor. By introducing the trifluoromethyl group into chemical structure, fuzuloparib exhibits higher stability and lower inter-individual variability than other PARP inhibitors. Several clinical trials (FZOCUS series and others) have been carried out to assess the efficacy and safety of fuzuloparib through different lines of treatments for advanced or recurrent ovarian cancer in both treatment and maintenance. Here, we present the most recent data from these studies, discuss current progress and potential future directions.
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    Over the last decade, clinical trials using various poly ADP ribose polymerase (PARP) inhibitors on patients with ovarian cancer have shown promising results. The introduction of PARP inhibitors has changed the treatment landscape and improved outcome...

    Over the last decade, clinical trials using various poly ADP ribose polymerase (PARP) inhibitors on patients with ovarian cancer have shown promising results. The introduction of PARP inhibitors has changed the treatment landscape and improved outcomes for patients with ovarian cancer. Fuzuloparib, developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd., is a novel orally available small molecule PARP inhibitor. By introducing the trifluoromethyl group into chemical structure, fuzuloparib exhibits higher stability and lower inter-individual variability than other PARP inhibitors. Several clinical trials (FZOCUS series and others) have been carried out to assess the efficacy and safety of fuzuloparib through different lines of treatments for advanced or recurrent ovarian cancer in both treatment and maintenance. Here, we present the most recent data from these studies, discuss current progress and potential future directions.

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    참고문헌 (Reference)

    1 Murai J, "Trapping of PARP1 and PARP2 by clinical PARP inhibitors" 72 : 5588-5599, 2012

    2 Ivy SP, "The ‘Pushmi-Pullyu’ of DNA REPAIR : clinical synthetic lethality" 2 : 646-656, 2016

    3 Javle M, "The role of PARP in DNA repair and its therapeutic exploitation" 105 : 1114-1122, 2011

    4 Coleman RL, "Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy(ARIEL3) : a randomised, double-blind, placebo-controlled, phase 3 trial" 390 : 1949-1961, 2017

    5 Li J, "Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction" 34 : 1448-1454, 2016

    6 Lai H, "Protein panel of serum-derived small extracellular vesicles for the screening and diagnosis of epithelial ovarian cancer" 14 : 3719-, 2022

    7 Horton JK, "Predicting enhanced cell killing through PARP inhibition" 11 : 13-18, 2013

    8 Li H, "Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib(SHR3162), in patients with advanced solid tumors" 32 : 370-382, 2020

    9 Wang L, "Pharmacologic characterization of fluzoparib, a novel poly(ADP-ribose)polymerase inhibitor undergoing clinical trials" 110 : 1064-1075, 2019

    10 Sachdev E, "PARP inhibition in cancer : an update on clinical development" 14 : 657-679, 2019

    1 Murai J, "Trapping of PARP1 and PARP2 by clinical PARP inhibitors" 72 : 5588-5599, 2012

    2 Ivy SP, "The ‘Pushmi-Pullyu’ of DNA REPAIR : clinical synthetic lethality" 2 : 646-656, 2016

    3 Javle M, "The role of PARP in DNA repair and its therapeutic exploitation" 105 : 1114-1122, 2011

    4 Coleman RL, "Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy(ARIEL3) : a randomised, double-blind, placebo-controlled, phase 3 trial" 390 : 1949-1961, 2017

    5 Li J, "Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction" 34 : 1448-1454, 2016

    6 Lai H, "Protein panel of serum-derived small extracellular vesicles for the screening and diagnosis of epithelial ovarian cancer" 14 : 3719-, 2022

    7 Horton JK, "Predicting enhanced cell killing through PARP inhibition" 11 : 13-18, 2013

    8 Li H, "Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib(SHR3162), in patients with advanced solid tumors" 32 : 370-382, 2020

    9 Wang L, "Pharmacologic characterization of fluzoparib, a novel poly(ADP-ribose)polymerase inhibitor undergoing clinical trials" 110 : 1064-1075, 2019

    10 Sachdev E, "PARP inhibition in cancer : an update on clinical development" 14 : 657-679, 2019

    11 Rouleau M, "PARP inhibition : PARP1 and beyond" 10 : 293-301, 2010

    12 Liu JF, "Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer" 30 : 551-557, 2019

    13 Penson RT, "Olaparib versus nonplatinum chemotherapy in patients with platinum-sensitive relapsed ovarian cancer and a germline BRCA1/2 mutation(SOLO3) : a randomized phase III trial" 38 : 1164-1174, 2020

    14 Pujade-Lauraine E, "Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation(SOLO2/ENGOT-Ov21) : a double-blind, randomised, placebo-controlled, phase 3 trial" 18 : 1274-1284, 2017

    15 Ray-Coquard I, "Olaparib plus bevacizumab as first-line maintenance in ovarian cancer" 381 : 2416-2428, 2019

    16 Ledermann J, "Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer" 366 : 1382-1392, 2012

    17 Mirza MR, "Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer(NSGO-AVANOVA2/ENGOT-ov24) : a randomised, phase 2, superiority trial" 20 : 1409-1419, 2019

    18 Mirza MR, "Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer" 375 : 2154-2164, 2016

    19 Giornelli GH, "Management of relapsed ovarian cancer : a review" 5 : 1197-, 2016

    20 Hegan DC, "Inhibition of poly(ADP-ribose)polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130" 107 : 2201-2206, 2010

    21 Bindra RS, "Hypoxia-induced down-regulation of BRCA1 expression by E2Fs" 65 : 11597-11604, 2005

    22 Konstantinopoulos PA, "Homologous recombination deficiency : exploiting the fundamental vulnerability of ovarian cancer" 5 : 1137-1154, 2015

    23 Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" 71 : 209-249, 2021

    24 Li N, "Fuzuloparib maintenance therapy in patients with platinum-sensitive, recurrent ovarian carcinoma(FZOCUS-2) : a multicenter, randomized, double-blind, placebo-controlled, phase III trial" 40 : 2436-2446, 2022

    25 Lee A, "Fuzuloparib : first approval" 81 : 1221-1226, 2021

    26 Lheureux S, "Epithelial ovarian cancer" 393 : 1240-1253, 2019

    27 Domchek SM, "Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy" 140 : 199-203, 2016

    28 Bindra RS, "Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells" 24 : 8504-8518, 2004

    29 Liu JF, "Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer : a randomised phase 2 study" 15 : 1207-1214, 2014

    30 International Agency for Research on Cancer (IARC), "Cancer today" World Health Organization

    31 Oza AM, "Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation : Integrated analysis of data from Study 10 and ARIEL2" 147 : 267-275, 2017

    32 Li N, "An open-label, multicenter, single-arm, phase II study of fuzuloparib in patients with germline BRCA1/2 mutation and platinum-sensitive recurrent ovarian cancer" 27 : 2452-2458, 2021

    33 Wang YQ, "An Update on poly(ADP-ribose)polymerase-1(PARP-1)inhibitors : opportunities and challenges in cancer therapy" 59 : 9575-9598, 2016

    34 Li H, "A phase 1 trial of the PARP inhibitor fuzuloparib in combination with the anti-angiogenic apatinib in recurrent ovarian or triple-negative breast cancer" 40 16 (40 16): 5539-, 2022

    35 Chan N, ""Contextual"synthetic lethality and/or loss of heterozygosity : tumor hypoxia and modification of DNA repair" 16 : 4553-4560, 2010

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