• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

PARP-1抑制剂与其他药物联用克服耐药性的研究进展

施锦渝, 柏英, 彭珂文, 张文慧, 朱启华, 徐云根

施锦渝, 柏英, 彭珂文, 张文慧, 朱启华, 徐云根. PARP-1抑制剂与其他药物联用克服耐药性的研究进展[J]. 中国药科大学学报, 2019, 50(5): 523-530. DOI: 10.11665/j.issn.1000-5048.20190503
引用本文: 施锦渝, 柏英, 彭珂文, 张文慧, 朱启华, 徐云根. PARP-1抑制剂与其他药物联用克服耐药性的研究进展[J]. 中国药科大学学报, 2019, 50(5): 523-530. DOI: 10.11665/j.issn.1000-5048.20190503
shu
SHI Jinyu, BAI Ying, PENG Kewen, ZHANG Wenhui, ZHU Qihua, XU Yungen. Research progress of PARP-1 inhibitors in combination with other drugs to overcome drug resistance[J]. Journal of China Pharmaceutical University, 2019, 50(5): 523-530. DOI: 10.11665/j.issn.1000-5048.20190503
Citation: SHI Jinyu, BAI Ying, PENG Kewen, ZHANG Wenhui, ZHU Qihua, XU Yungen. Research progress of PARP-1 inhibitors in combination with other drugs to overcome drug resistance[J]. Journal of China Pharmaceutical University, 2019, 50(5): 523-530. DOI: 10.11665/j.issn.1000-5048.20190503
shu

PARP-1抑制剂与其他药物联用克服耐药性的研究进展

  • 中国药科大学药物化学系

基金项目: 国家自然科学基金资助项目(No.81502928)；江苏高等学校优秀科技创新团队资助项目(2015)

Research progress of PARP-1 inhibitors in combination with other drugs to overcome drug resistance

摘要

    摘要
  • 摘要: 聚腺苷二磷酸核糖聚合酶-1(PARP-1)在DNA修复和细胞凋亡中发挥着至关重要的作用，PARP-1抑制剂在肿瘤治疗领域取得了突破性的进展，但耐药性的出现限制了其在临床上的进一步应用。本文就PARP-1抑制剂与其他药物联用克服耐药性的研究进展进行了综述，重点介绍了临床上现有的药物组合方法及其疗效，并对药物联用策略进行了评价与展望，提出双靶点或多靶点药物的开发将成为克服PARP-1抑制剂耐药性、拓宽适应证的新思路。
    Abstract: Poly(ADP-ribose)polymerase-1(PARP-1)plays a vital role in the regulation of DNA repair and apoptosis. Breakthrough has been made in the treatment of cancer with PARP-1 inhibitors, but the emergence of drug resistance has limited its further application in clinic. This paper reviews advances in the research on PARP-1 inhibitors combined with other drugs to overcome drug resistance, highlights and evaluates the existing drug combination strategies and their therapeutic effects in clinical practice. It is proposed that the development of dual-target or multi-target drugs will become a promising approach to overcome the resistance of PARP-1 inhibitors and broaden their indications.
    • HTML全文
    • 参考文献(56)
  • [1] Vyas S,Chang P.New PARP targets for cancer therapy[J].Nat Rev Cancer,2014,14(7):502-509.
    [2] Krishnakumar R, Kraus WL. The PARP side of the nucleus:molecular actions,physiological outcomes,and clinical targets[J].Mol Cell,2010,39(1):8-24.
    [3] Miwa M,Masutani M.Poly ADP-ribosylation and cancer[J].Cancer Sci,2007,98(10):1528-1535.
    [4] Chen A.PARP inhibitors:its role in treatment of cancer[J].Chin J Cancer,2011,30(7):463-471.
    [5] Lord CJ, Ashworth A. The DNA damage response and cancer therapy[J].Nature,2012,481(7381):287-294.
    [6] Murai J, Huang SY, Das BB, et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors[J].Cancer Res,2012,72(21):5588-5599.
    [7] Zhao N,Sun HB.Poly(ADP-ribose)polymerase inhibitors and synthetic lethality[J].J China Pharm Univ(中国药科大学学报),2012,43(2):107-112.
    [8] Wang YQ,Wang PY,Wang YT,et al.An update on poly(ADP-ribose)polymerase-1(PARP-1)inhibitors:opportunities and challenges in cancer therapy[J].J Med Chem,2016,59(21):9575-9598.
    [9] Damia G, D′Incalci M. Targeting DNA repair as a promising approach in cancer therapy[J].Eur J Cancer,2007,43(12):1791-1801.
    [10] Peralta-Leal A,Rodríguez-Vargas JM,Aguilar-Quesada R,et al.PARP inhibitors:new partners in the therapy of cancer and inflammatory diseases[J].Free Radic Biol Med,2009,47(1):13-26.
    [11] Konstantinopoulos PA,Ceccaldi R,Shapiro GI,et al.Homologous recombination deficiency:exploiting the fundamental vulnerability of ovarian cancer[J].Cancer Discov,2015,5(11):1137-1154.
    [12] Lord CJ,Ashworth A.Mechanisms of resistance to therapies targeting BRCA-mutant cancers[J].Nat Med,2013,19(11):1381-1388.
    [13] Bunting SF,Callén E,Wong N,et al.53BP1 inhibits homologous recombination in brca1-deficient cells by blocking resection of DNA breaks[J].Cell,2010,141(2):243-254.
    [14] Bouwman P,Aly A,Escandell JM,et al.53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers[J].Nat Struct Mol Biol,2010,17(6):688-695.
    [15] Xu GT,Chapman JR,Brandsma I,et al.REV7 counteracts DNA double-strand break resection and affects PARP inhibition[J].Nature,2015,521(7553):541-544.
    [16] Boersma V,Moatti N,Segura-Bayona S,et al.MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5′end resection[J].Nature,2015,521(7553):537-540.
    [17] Choi YH,Yu AM.ABC transporters in multidrug resistance and pharmacokinetics,and strategies for drug development[J].Curr Pharm Des,2014,20(5):793-807.
    [18] Rottenberg S,Jaspers JE,Kersbergen A,et al.High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs[J].Proc Natl Acad Sci U S A,2008,105(44):17079-17084.
    [19] Oplustilova L,Wolanin K,Mistrik M,et al.Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment[J].Cell Cycle,2012,11(20):3837-3850.
    [20] Vaidyanathan A,Sawers L,Gannon AL,et al.ABCB1(MDR1)induction defines a common resistance mechanism in paclitaxel-and olaparib-resistant ovarian cancer cells[J].Br J Cancer,2016,115(4):431-441.
    [21] BiPar sciences presents interim phase 2 results for PARP inhibitor BSI-201 at San Antonio Breast Cancer Symposium[J].Cancer Biol Ther,2009,8(1):2-3.
    [22] Kummar S,Ji JP,Morgan R,et al.A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas[J].Clin Cancer Res,2012,18(6):1726-1734.
    [23] Kummar S,Chen A,Ji JP,et al.Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas[J].Cancer Res,2011,71(17):5626-5634.
    [24] Samol J,Ranson M,Scott E,et al.Safety and tolerability of the poly(ADP-ribose)polymerase(PARP)inhibitor,olaparib(AZD2281)in combination with topotecan for the treatment of patients with advanced solid tumors:a phase I study[J].Invest New Drugs,2012,30(4):1493-1500.
    [25] Neri P,Ren L,Gratton K,et al.Bortezomib-induced “BRCAness” sensitizes multiple myeloma cells to PARP inhibitors[J].Blood,2011,118(24):6368-6379.
    [26] Grünwald V,Merseburger AS.The progression free survival-plateau with vascular endothelial growth factor receptor inhibitors:is there more to come[J]?Eur J Cancer,2013,49(11):2504-2511.
    [27] Lee JM,Trepel JB,Choyke P,et al.CECs and IL-8 have prognostic and predictive utility in patients with recurrent platinum-sensitive ovarian cancer:biomarker correlates from the randomized phase-2 trial of olaparib and cediranib compared with olaparib in recurrent platinum-sensitive ovarian cancer[J].Front Oncol,2015,5:123.
    [28] Liu JF,Tolaney SM,Birrer M,et al.A phase 1 trial of the poly(ADP-ribose)polymerase inhibitor olaparib(AZD2281)in combination with the anti-angiogenic cediranib(AZD2171)in recurrent epithelial ovarian or triple-negative breast cancer[J].Eur J Cancer,2013,49(14):2972-2978.
    [29] Gelmon KA,Tischkowitz M,MacKay H,et al.Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer:a phase 2,multicentre,open-label,non-randomised study[J].Lancet Oncol,2011,12(9):852-861.
    [30] Liu JF,Barry WT,Birrer M,et al.Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer:a randomised phase 2 study[J].Lancet Oncol,2014,15(11):1207-1214.
    [31] Lim S,Kaldis P.Cdks,cyclins and CKIs:roles beyond cell cycle regulation[J].Development,2013,140(15):3079-3093.
    [32] Asghar U, Witkiewicz AK, Turner NC, et al. The history and future of targeting cyclin-dependent kinases in cancer therapy[J].Nat Rev Drug Discov,2015,14(2):130-146.
    [33] Cicenas J,Kalyan K,Sorokinas A,et al.Highlights of the latest advances in research on CDK inhibitors[J].Cancers(Basel),2014,6(4):2224-2242.
    [34] Canavese M,Santo L,Raje N.Cyclin dependent kinases in cancer[J].Cancer Biol Ther,2012,13(7):451-457.
    [35] Blazek D,Kohoutek J,Bartholomeeusen K,et al.The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes[J].Genes Dev,2011,25(20):2158-2172.
    [36] Liang KW,Gao X,Gilmore JM,et al.Characterization of human cyclin-dependent kinase 12(CDK12)and CDK13 complexes in C-terminal domain phosphorylation,gene transcription,and RNA processing[J].Mol Cell Biol,2015,35(6):928-938.
    [37] Joshi PM,Sutor SL,Huntoon CJ,et al.Ovarian cancer-associated mutations disable catalytic activity of CDK12,a kinase that promotes homologous recombination repair and resistance to cisplatin and poly(ADP-ribose)polymerase inhibitors[J].J Biol Chem,2014,289(13):9247-9253.
    [38] Johnson SF, Cruz C, Greifenberg AK, et al. CDK12 inhibition reverses de novo and acquired PARP inhibitor resistance in BRCA wild-type and mutated models of triple-negative breast cancer[J].Cell Rep,2016,17(9):2367-2381.
    [39] Lim E,Johnson SF,Geyer M,et al.Sensitizing HR-proficient cancers to PARP inhibitors[J].Mol Cell Oncol,2017,4(6):e1299272.doi: 10.1080/23723556.2017.1299272.
    [40] Johnson SF, Cruz C, Greifenberg AK, et al. CDK12 inhibition reverses de novo and acquired PARP inhibitor resistance in BRCA wild-type and mutated models of triple-negative breast cancer[J].Cell Rep,2016,17(9):2367-2381.
    [41] Johnson N,Cai DP,Kennedy RD,et al.Cdk1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damage[J].Mol Cell,2009,35(3):327-339.
    [42] Johnson N,Li YC,Walton ZE,et al.Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition[J].Nat Med,2011,17(7):875-882.
    [43] Bolin C, Boudra MT, Fernet M, et al. The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose)polymerase activity and responses to radiation[J].Cell Mol Life Sci,2012,69(6):951-962.
    [44] Tominaga Y,Li CL,Wang RH,et al.Murine Wee1 plays a critical role in cell cycle regulation and pre-implantation stages of embryonic development[J].Int J Biol Sci,2006,2(4):161-170.
    [45] Karnak D,Engelke CG,Parsels LA,et al.Combined inhibition of Wee1 and PARP1/2 for radiosensitization in pancreatic cancer[J].Clin Cancer Res,2014,20(19):5085-5096.
    [46] Garcia TB, Snedeker JC, Baturin D, et al. A small-molecule inhibitor of WEE1,AZD1775,synergizes with olaparib by impairing homologous recombination and enhancing DNA damage and apoptosis in acute leukemia[J].Mol Cancer Ther,2017,16(10):2058-2068.
    [47] Parsels LA,Karnak D,Parsels JD,et al.PARP1 trapping and DNA replication stress enhance radiosensitization with combined WEE1 and PARP inhibitors[J].Mol Cancer Res,2018,16(2):222-232.
    [48] Kumar A,Fernandez-Capetillo O,Fernadez-Capetillo O,et al.Nuclear phosphoinositide 3-kinase beta controls double-strand break DNA repair[J].Proc Natl Acad Sci U S A,2010,107(16):7491-7496.
    [49] Ibrahim YH, García-García C, Serra V, et al. PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition[J].Cancer Discov,2012,2(11):1036-1047.
    [50] Wang D,Li CB,Zhang Y,et al.Combined inhibition of PI3K and PARP is effective in the treatment of ovarian cancer cells with wild-type PIK3CA genes[J].Gynecol Oncol,2016,142(3):548-556.
    [51] Juvekar A,Burga LN,Hu H,et al.Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer[J].Cancer Discov,2012,2(11):1048-1063.
    [52] Sun CY,Fang Y,Yin J,et al.Rational combination therapy with PARP and MEK inhibitors capitalizes on therapeutic liabilities in RAS mutant cancers[J].Sci Transl Med,2017,9(392):eaal5148.
    [53] Medová M,Aebersold DM,Zimmer Y.MET inhibition in tumor cells by PHA665752 impairs homologous recombination repair of DNA double strand breaks[J].Int J Cancer,2012,130(3):728-734.
    [54] Du Y,Yamaguchi H,Wei YK,et al.Corrigendum:Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors[J].Nat Med,2016,22(10):1192.
    [55] Henneman L,van Miltenburg MH,Michalak EM,et al.Selective resistance to the PARP inhibitor olaparib in a mouse model for BRCA1-deficient metaplastic breast cancer[J].Proc Natl Acad Sci U S A,2015,112(27):8409-8414.
    [56] Sun Y,Carlson JH,Lin X,et al.Abstract P3-14-08:Preclinical efficacy of targeting c-MET by ARQ197 in combination with PARP inhibitor plus standard cytotoxic agent in triple-negative breast cancer cell lines[C]//Poster Session Abstracts,American Association for Cancer Research,2016.
    • 相关文章
    • 施引文献
    • 资源附件(0)
计量
  • 文章访问数:  778
  • HTML全文浏览量:  8
  • PDF下载量:  1553
  • 被引次数: 0
出版历程
  • 刊出日期:  2019-10-24

目录

摘要
HTML全文
    参考文献(56)
    相关文章
    施引文献
    资源附件(0)

    /

    返回文章
    返回

    版权所有：《中国药科大学学报》编辑部苏ICP备05007142号

    地址：江苏省南京市鼓楼区童家巷24号（210009）电话: 025-83271566E-mail: xuebao@cpu.edu.cn

    本系统由 北京仁和汇智信息技术有限公司 开发  百度统计

    访问量：336053

    x 关闭 永久关闭