口服PARP抑制剂——talazoparib
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摘要
Talazoparib是一种多聚二磷酸腺苷核糖聚合酶(poly ADP-Ribose polymerase,PARP)抑制剂,用于存在生殖系BRCA突变(gBRCAm)、HER2阴性局部晚期或转移性乳腺癌(metastatic breast cancer, MBC)患者的治疗。Talazoparib是目前报道中发现的最强PARP抑制剂,业界对其非常看好,其在卵巢癌等其他适应证方面的研究也值得期待。笔者就talazoparib的基本性质、作用机制、药动学、药效学、临床试验及应用等研发动态作一概述,以期为临床用药起到指导作用。
Talazoparib is a poly ADP-Ribose polymerase(PARP) inhibitor indicated for the treatment of adult patients with germline BRCAmutated(gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Talazoparib is the strongest PARP inhibitor found in the current reports. People generally believe that the future of talazoparib is promising, and the studies of talazoparib in ovarian cancer and other indications are also really to be expected. In this paper, the development process, properties, mechanism, pharmacokinetics, pharmacodynamics, clinical trials and applications of talazoparib are summarized, in order to provide reference for clinical treatment.
Talazoparib is a poly ADP-Ribose polymerase(PARP) inhibitor indicated for the treatment of adult patients with germline BRCAmutated(gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Talazoparib is the strongest PARP inhibitor found in the current reports. People generally believe that the future of talazoparib is promising, and the studies of talazoparib in ovarian cancer and other indications are also really to be expected. In this paper, the development process, properties, mechanism, pharmacokinetics, pharmacodynamics, clinical trials and applications of talazoparib are summarized, in order to provide reference for clinical treatment.
引文
[1]李贺,郑荣寿,张思维,等.2014年中国女性乳腺癌发病与死亡分析[J].中华肿瘤杂志,2018,40(3):166-170.
[2] Parisi M,Pelletier C,Cherepanov D,et al. Outcomes research examining treatments, quality of life and costs in HER2-negative and triple-negative metastatic breast cancer:a systematic literature review[J]. Journal of Comparative Effectiveness Research,2018,7(4):2017-2020.
[3]王凌霄.PARP-1抑制剂的设计、合成与生物活性评价[D].北京:中国人民解放军军事医学科学院,2016.
[4] Shen Y, Aoyagischarber M,Wang B. Trapping poly(ADP-Ribose)polymerase[J]. J Pharmacol Exp Ther, 2015,353(3):446-457.
[5] Talazoparib说明书.[EB/OL].(2018-10-16)[2018-12-20].https://www. accessdata. fda. gov/drugsatfda_docs/label/2018/211651s0001bl.pdf.
[6] Scott C L,Swisher E M,Kaufmann S H. Poly(ADP-Ribose)polymerase inhibitors:recent advances and future development[J]. J Clin Oncol,2015,33(12):1397-1406.
[7] Brown J S,Kaye S B, Yap T A. PARP inhibitors:the race is on[J]. Br J Cancer,2016,114(7):713-715.
[8] Rugo H S,Ettl J,Woodward N E,et al. EMBRACA:efficacy outcomes in clinically relevant subgroups comparing talazoparib(TALA),an oral poly ADP ribose polymerase(PARP)inhibitor,to physician's choice of therapy(PCT)in patients with advanced breast cancer and a germline BRCA mutation[J]. J Clin Oncol,2018,36(Suppl 15):S1069.
[9] Pignata S,C Cecere S,Du Bois A,et al. Treatment of recurrent ovarian cancer[J]. Ann Oncol,2017,28(Suppl 8):Sviii51-Sviii56.
[10] Mittica G,Ghisoni E,Giannone G,et al. PARP inhibitors in ovarian cancer[J]. Recent Pat Anticancer Drug Discov, 2018,13(4):392-410.
[2] Parisi M,Pelletier C,Cherepanov D,et al. Outcomes research examining treatments, quality of life and costs in HER2-negative and triple-negative metastatic breast cancer:a systematic literature review[J]. Journal of Comparative Effectiveness Research,2018,7(4):2017-2020.
[3]王凌霄.PARP-1抑制剂的设计、合成与生物活性评价[D].北京:中国人民解放军军事医学科学院,2016.
[4] Shen Y, Aoyagischarber M,Wang B. Trapping poly(ADP-Ribose)polymerase[J]. J Pharmacol Exp Ther, 2015,353(3):446-457.
[5] Talazoparib说明书.[EB/OL].(2018-10-16)[2018-12-20].https://www. accessdata. fda. gov/drugsatfda_docs/label/2018/211651s0001bl.pdf.
[6] Scott C L,Swisher E M,Kaufmann S H. Poly(ADP-Ribose)polymerase inhibitors:recent advances and future development[J]. J Clin Oncol,2015,33(12):1397-1406.
[7] Brown J S,Kaye S B, Yap T A. PARP inhibitors:the race is on[J]. Br J Cancer,2016,114(7):713-715.
[8] Rugo H S,Ettl J,Woodward N E,et al. EMBRACA:efficacy outcomes in clinically relevant subgroups comparing talazoparib(TALA),an oral poly ADP ribose polymerase(PARP)inhibitor,to physician's choice of therapy(PCT)in patients with advanced breast cancer and a germline BRCA mutation[J]. J Clin Oncol,2018,36(Suppl 15):S1069.
[9] Pignata S,C Cecere S,Du Bois A,et al. Treatment of recurrent ovarian cancer[J]. Ann Oncol,2017,28(Suppl 8):Sviii51-Sviii56.
[10] Mittica G,Ghisoni E,Giannone G,et al. PARP inhibitors in ovarian cancer[J]. Recent Pat Anticancer Drug Discov, 2018,13(4):392-410.