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聚(ADP-核糖)聚合酶抑制剂在胰腺癌中的应用。

Poly(ADP-ribose) polymerase inhibition in pancreatic cancer.

机构信息

Department of Medical Oncology, Heidelberg University Hospital, National Center for Tumor Diseases, Heidelberg, Germany.

Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.

出版信息

Genes Chromosomes Cancer. 2021 May;60(5):373-384. doi: 10.1002/gcc.22932. Epub 2021 Jan 9.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment options. Recently, the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib has been approved for maintenance therapy after successful platinum-based chemotherapy in patients with germline mutations in BRCA1 and BRCA2. Approval was based on the POLO study that has shown a significant improvement in progression-free survival for patients with metastatic PDAC after at least 4 months of platinum-based chemotherapy. Hopefully, this first biomarker-directed targeted therapy for a relevant subgroup of pancreatic cancer patients is only the beginning of an era of personalized therapy for pancreatic cancer. The potential role for PARPi in improving survival in patients with pancreatic cancer containing somatic tumor mutations has yet to be established. Multiple studies investigating whether PARPi therapy might benefit a larger group of pancreatic cancer patients with homologous recombination repair deficiency and whether combinations with chemotherapy, immunotherapy, or small molecules can improve efficacy are currently underway. We here review the molecular basis for PARPi therapy in PDAC patients and recent developments in clinical studies.

摘要

胰腺导管腺癌 (PDAC) 是一种致命疾病,治疗选择有限。最近,聚 (ADP-核糖) 聚合酶抑制剂 (PARPi) 奥拉帕利已被批准用于 BRCA1 和 BRCA2 种系突变的患者在成功接受基于铂的化疗后的维持治疗。批准基于 POLO 研究,该研究表明,在接受至少 4 个月基于铂的化疗后,转移性 PDAC 患者的无进展生存期有显著改善。希望这是针对相关亚组胰腺癌患者的首个基于生物标志物的靶向治疗,仅仅是胰腺癌个体化治疗时代的开始。PARPi 是否有可能改善具有体细胞肿瘤突变的胰腺癌患者的生存,这一潜力尚未得到证实。目前正在进行多项研究,旨在探讨 PARPi 治疗是否可能使更多具有同源重组修复缺陷的胰腺癌患者受益,以及与化疗、免疫疗法或小分子联合使用是否可以提高疗效。我们在此回顾了 PARPi 治疗 PDAC 患者的分子基础以及临床研究的最新进展。

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