复发性卵巢癌新药PARP抑制剂niraparib
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摘要
近年研究表明,聚腺苷二磷酸核糖聚合酶(PARP)抑制剂在乳腺癌易感基因(BRCA)突变的乳腺癌和卵巢癌患者中可明显延长无瘤生存期。2017年3月27日,FDA加快批准PARP抑制剂niraparib用于对铂类药物化疗完全响应或部分响应的上皮卵巢癌、输卵管或原发性腹膜癌的成年复发患者的维持治疗。本文从理化特性、临床前研究和临床研究等方面介绍该首个批准用于卵巢癌维持疗法的PARP抑制剂niraparib,以期为临床医生和卵巢癌患者选择治疗方法提供参考。
Recent studies have shown that poly(ADP-ribose) polymerase(PARP) inhibitors significantly prolong the progression-free survival in the patients with breast cancer and ovarian cancer with the breast cancer susceptibility gene(BRCA) mutations. On March 27,2017,FDA accelerated the approval of the PAPR inhibitor niraparib for the maintenance treatment of adult patients with recurrent epithelial ovarian,fallopian tube,or primary peritoneal cancer who were in complete or partial response to platinum-based chemotherapy. In this paper,we introduced niraparib,the first PARP inhibitor for the maintenance therapy of recurrent ovarian cancer,from the aspects of physicochemical properties,preclinical studies and clinical studies,in order to provide reference for doctors and patients with ovarian cancer.
Recent studies have shown that poly(ADP-ribose) polymerase(PARP) inhibitors significantly prolong the progression-free survival in the patients with breast cancer and ovarian cancer with the breast cancer susceptibility gene(BRCA) mutations. On March 27,2017,FDA accelerated the approval of the PAPR inhibitor niraparib for the maintenance treatment of adult patients with recurrent epithelial ovarian,fallopian tube,or primary peritoneal cancer who were in complete or partial response to platinum-based chemotherapy. In this paper,we introduced niraparib,the first PARP inhibitor for the maintenance therapy of recurrent ovarian cancer,from the aspects of physicochemical properties,preclinical studies and clinical studies,in order to provide reference for doctors and patients with ovarian cancer.
引文
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[2]刘琦.卵巢癌治疗的决策[J].医学研究生学报,2010,3(11):1123-1126.
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[5]JONES P,WILCOXEN K,ROVLEY M,et al.Niraparib:a poly(ADP-ribose)polymerase(PARP)inhibitor for the treatment of tumors with defective homologous recombination[J].J Med Chem,2015,58(8):3302-3314.
[6]WANG L,MASON KA,ANG KK,et al.MK-4827,a PARP-1/-2 inhibitor,strongly enhances response of human lung and breast cancer xenografts to radiation[J].Invest New Drugs,2012,30(6):2213-2220.
[7]GENTHER WS,KUZNICKI AM,ANDRADE P,et al.Treatment with the PARP inhibitor,niraparib,sensitizes colorectal cancer cell lines to irinotecan regardless of MSI/MSS status[J].Cancer Cell Int,2015,15(1):14.
[8]SANDHU SK,SCHELMAN WR,WILDING G,et al.The poly(ADP-ribose)polymerase inhibitor niraparib(MK4827)in BRCA mutation carriers and patients with sporadic cancer:a phase 1 dose-escalation trail[J].Lancet Oncol,2013,14(9):882-892.
[9]MIRZA MR,MONK BJ,HERRSTEDT J,et al.Niraparib maintenance therapy in platinum-sensitive,recurrent ovarian cancer[J].N Egnl J Med,2016,22(357):2154-2164.
[10]井潇,吴纯启,王茜莎,等.药物肝损伤的毒性通路及分子起始事件的研究进展[J].中国新药杂志,2016,25(12):1348-1354.
[11]刘小茜,吴文晓,耿兴超,等.药物性肝损伤生物标志物研究进展[J].中国新药杂志,2018,27(1):47-52.
[2]刘琦.卵巢癌治疗的决策[J].医学研究生学报,2010,3(11):1123-1126.
[3]MUNROE M,KOLESAR J.Olaparib for the treatment of BRCAmutated advanced ovarian cancer[J].Am J Health Syst Pharm,2016,73(14):1037-1041.
[4]SCOTT LJ.Niraparib:first global approval[J].Drugs,2017,77(9):1029-1034.
[5]JONES P,WILCOXEN K,ROVLEY M,et al.Niraparib:a poly(ADP-ribose)polymerase(PARP)inhibitor for the treatment of tumors with defective homologous recombination[J].J Med Chem,2015,58(8):3302-3314.
[6]WANG L,MASON KA,ANG KK,et al.MK-4827,a PARP-1/-2 inhibitor,strongly enhances response of human lung and breast cancer xenografts to radiation[J].Invest New Drugs,2012,30(6):2213-2220.
[7]GENTHER WS,KUZNICKI AM,ANDRADE P,et al.Treatment with the PARP inhibitor,niraparib,sensitizes colorectal cancer cell lines to irinotecan regardless of MSI/MSS status[J].Cancer Cell Int,2015,15(1):14.
[8]SANDHU SK,SCHELMAN WR,WILDING G,et al.The poly(ADP-ribose)polymerase inhibitor niraparib(MK4827)in BRCA mutation carriers and patients with sporadic cancer:a phase 1 dose-escalation trail[J].Lancet Oncol,2013,14(9):882-892.
[9]MIRZA MR,MONK BJ,HERRSTEDT J,et al.Niraparib maintenance therapy in platinum-sensitive,recurrent ovarian cancer[J].N Egnl J Med,2016,22(357):2154-2164.
[10]井潇,吴纯启,王茜莎,等.药物肝损伤的毒性通路及分子起始事件的研究进展[J].中国新药杂志,2016,25(12):1348-1354.
[11]刘小茜,吴文晓,耿兴超,等.药物性肝损伤生物标志物研究进展[J].中国新药杂志,2018,27(1):47-52.