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中国临床药理学与治疗学 ›› 2022, Vol. 27 ›› Issue (1): 108-115.doi: 10.12092/j.issn.1009-2501.2022.01.015

• 综述与讲座 • 上一篇    下一篇

聚腺苷二磷酸-核糖聚合酶抑制剂在胰腺癌中的研究进展

郑 莹1,张 玲1,姚 丽1,王乾合1,朱克祥1,2   

  1. 1兰州大学第一临床医学院,兰州 730000,甘肃;2兰州大学第一医院普外科,兰州 730000,甘肃
  • 收稿日期:2021-09-13 修回日期:2021-12-11 出版日期:2022-01-26 发布日期:2022-02-09
  • 通讯作者: 朱克祥,男,博士,主任医师,研究方向: 肝胆胰方向。 E-mail: flexzhu6910@sina.com
  • 作者简介:郑莹,女,住院医师,硕士在读,研究方向:肝胆胰方向。 Tel:17352120498 E-mail:18368142836@163.com
  • 基金资助:
    国家自然科学基金(81960516)

Research progress of PARP inhibitors in pancreatic cancer

ZHENG Ying1, ZHANG Ling1, YAO Li1, WANG Qianhe1, ZHU Kexiang1,2   

  1. 1 The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu, China
  • Received:2021-09-13 Revised:2021-12-11 Online:2022-01-26 Published:2022-02-09

摘要: 胰腺癌是一种高度恶性的肿瘤,聚腺苷二磷酸-核糖聚合酶(PARP)抑制剂(PARPI)是首类基于合成致死概念开发合成的抗肿瘤药物,并被临床批准用于卵巢癌和乳腺癌的治疗。由于特定的DNA修复缺陷,研究发现具有BRCA1/2种系突变的肿瘤对PARPI敏感,但具体的作用机制仍不十分清楚。目前针对胰腺癌的多项临床试验已经开展,III期POLO研究表明Olaparib在种系BRCA1/2突变患者和铂类诱导化疗后转移性胰腺癌患者中作为维持治疗有效且耐受性良好。联合治疗的相关临床研究表明添加PARPI的益处很可能来自维持治疗阶段。总的来说,PARPI在胰腺癌治疗领域有广阔的前景。

关键词: 胰腺癌, PARP抑制剂, BRCA突变, 分子机制, 临床试验

Abstract: Pancreatic cancer is a highly malignant tumor. PARP inhibitor (PARPI) is the first synthetic antineoplastic drug developed based on the concept of synthetic lethality and has been clinically approved for the treatment of ovarian cancer and breast cancer. Due to specific DNA repair defects, studies have found that tumors with BRCA1/2 germline mutations are sensitive to PARPI, but the specific mechanism of action is still unclear. A number of clinical trials for pancreatic cancer have been carried out. Phase III POLO studies have shown that Olaparib is effective and well tolerated as a maintenance treatment in patients with germline BRCA1/2 mutations and patients with metastatic pancreatic cancer after platinum-based induction chemotherapy. Clinical studies related to combination therapy suggest that the benefit of adding PARPI is likely to come from the maintenance phase of treatment. In general, PARPI has broad prospects in the treatment of pancreatic cancer.

Key words: pancreatic cancer, PARP inhibitors, BRCA mutation, molecular mechanism, clinical trials

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