Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Expert Rev Gastroenterol Hepatol. 2024 Jan-Feb;18(1-3):55-72. doi: 10.1080/17474124.2024.2322648. Epub 2024 Feb 28.
Pancreas ductal adenocarcinoma (PDAC) is a frequently lethal malignancy that poses unique therapeutic challenges. The current mainstay of therapy for metastatic PDAC (mPDAC) is cytotoxic chemotherapy. NALIRIFOX (liposomal irinotecan, fluorouracil, leucovorin, oxaliplatin) is an emerging standard of care in the metastatic setting. An evolving understanding of PDAC pathogenesis is driving a shift toward targeted therapy. Olaparib, a poly-ADP-ribose polymerase (PARP) inhibitor, has regulatory approval for maintenance therapy in BRCA-mutated mPDAC along with other targeted agents receiving disease-agnostic approvals including for PDAC with rare fusions and mismatch repair deficiency. Ongoing research continues to identify and evaluate an expanding array of targeted therapies for PDAC.
This review provides a brief overview of standard therapies for PDAC and an emphasis on current and emerging targeted therapies.
There is notable potential for targeted therapies for mutated PDAC with opportunity for meaningful benefit for a sizable portion of patients with this disease. Further, emerging approaches are focused on novel immune, tumor microenvironment, and synthetic lethality strategies.
胰腺导管腺癌(PDAC)是一种常见的致命恶性肿瘤,具有独特的治疗挑战。目前转移性 PDAC(mPDAC)的主要治疗方法是细胞毒性化疗。NALIRIFOX(脂质体伊立替康、氟尿嘧啶、亚叶酸钙、奥沙利铂)是转移性疾病治疗中的新兴标准。对 PDAC 发病机制的不断深入了解正在推动靶向治疗的转变。奥拉帕利是一种聚 ADP-核糖聚合酶(PARP)抑制剂,已获得 BRCA 突变型 mPDAC 维持治疗的监管批准,以及其他针对包括 PDAC 罕见融合和错配修复缺陷在内的无疾病特异性批准的靶向药物。目前正在进行的研究继续识别和评估用于 PDAC 的靶向治疗的扩展。
本综述简要介绍了 PDAC 的标准治疗方法,并重点介绍了当前和新兴的靶向治疗方法。
对于突变型 PDAC 而言,靶向治疗具有显著的潜力,为该病的相当一部分患者带来了有意义的益处。此外,新兴方法专注于新型免疫、肿瘤微环境和合成致死性策略。