聚腺苷二磷酸-核糖聚合酶抑制剂在胰腺癌中的研究进展

Research progress of PARP inhibitors in pancreatic cancer

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。

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.