Dreyer Stephan B, Beer Philip, Hingorani Sunil R, Biankin Andrew V
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, UK.
West of Scotland Hepato-Biliary and Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK.
Nat Rev Clin Oncol. 2025 May 6. doi: 10.1038/s41571-025-01019-9.
Research studies aimed at improving the outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) have brought about limited progress, and in clinical practice, the optimized use of surgery, chemotherapy and supportive care have led to modest improvements in survival that have probably reached a plateau. As a result, PDAC is expected to be the second leading cause of cancer-related death in Western societies within a decade. The development of therapeutic advances in PDAC has been challenging owing to a lack of actionable molecular targets, a typically immunosuppressive microenvironment, and a disease course characterized by rapid progression and clinical deterioration. Yet, the progress in our understanding of PDAC and identification of novel therapeutic opportunities over the past few years is leading to a strong sense of optimism in the field. In this Perspective, we address the aforementioned challenges, including biological aspects of PDAC that make this malignancy particularly difficult to treat. We explore specific areas with potential for therapeutic advances, including targeting mutant KRAS, novel strategies to harness the antitumour immune response and approaches to early detection, and propose mechanisms to improve clinical trial design and to overcome various community and institutional barriers to progress.
旨在改善胰腺导管腺癌（PDAC）患者治疗效果的研究进展有限，在临床实践中，手术、化疗和支持治疗的优化使用仅使生存率有适度提高，且可能已达到平台期。因此，预计在十年内，PDAC将成为西方社会癌症相关死亡的第二大主要原因。由于缺乏可操作的分子靶点、典型的免疫抑制微环境以及以快速进展和临床恶化为特征的病程，PDAC治疗进展的发展一直具有挑战性。然而，过去几年我们对PDAC的认识进展以及新治疗机会的发现，让该领域产生了强烈的乐观情绪。在这篇观点文章中，我们阐述上述挑战，包括使这种恶性肿瘤特别难以治疗的PDAC生物学方面。我们探索具有治疗进展潜力的特定领域，包括靶向突变型KRAS、利用抗肿瘤免疫反应的新策略以及早期检测方法，并提出改善临床试验设计和克服各种阻碍进展的社区及机构障碍的机制。
