中国实用外科杂志

中国实用外科杂志

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胰腺癌治疗的未来——从单一靶点到系统生物学导向联合策略

楼文晖1，2   

  1. 1复旦大学附属中山医院胰腺外科，上海200032；2上海市老年医学中心普外科，上海 201104
  • 出版日期:2025-06-01

  • Online:2025-06-01

摘要： 胰腺癌恶性程度高，早期诊断手段缺乏，大多数病人确诊时已为不可切除晚期，5年生存率仅约13%。传统吉西他滨化疗及单一靶向（如EGFR抑制剂、KRAS抑制剂）治疗效果有限，主要因高密度胶原与癌相关成纤维细胞形成耐药屏障及肿瘤高度异质性。系统生物学整合多组学实现精准分子亚型划分，并结合网络药理学筛选多靶点联合方案，以克服耐药与免疫抑制微环境。数字孪生平台可模拟病人肿瘤进展与药物响应，指导个体化治疗优化。临床试验结果显示，KRAS G12D抑制剂MRTX1133、KRAS G12C抑制剂adagrasib与sotorasib及PARP抑制剂奥拉帕利在特定分子背景下具有协同抗肿瘤活性。多靶点联合策略配合人工智能与实时动态监测，有望提升胰腺癌治疗效果，改善预后。

关键词: 胰腺癌, 系统生物学, 多靶点治疗

Abstract: Pancreatic cancer is characterized by high malignancy and a lack of effective early diagnostic tools, resulting in most patients being diagnosed at an unresectable advanced stage, with a 5-year survival rate of approximately 13%. Traditional gemcitabine-based chemotherapy and single-targeted therapies (e.g., EGFR inhibitors, KRAS inhibitors) have shown limited efficacy, primarily due to the dense collagenous stroma and cancer-associated fibroblasts forming a drug-resistant barrier, as well as the high degree of tumor heterogeneity. Systems biology enables precise molecular subtyping through the integration of multi-omics data and, when combined with network pharmacology, facilitates the identification of multi-target combination strategies aimed at overcoming drug resistance and the immunosuppressive tumor microenvironment. Digital twin platforms can simulate tumor progression and drug responses in individual patients, thus guiding personalized therapeutic optimization. Clinical trials have demonstrated that KRAS G12D inhibitor MRTX1133, KRAS G12C inhibitors adagrasib and sotorasib, and the PARP inhibitor olaparib exhibit synergistic antitumor activity in specific molecular contexts. Multi-target combination strategies, in conjunction with artificial intelligence and real-time dynamic monitoring, hold promises for improving treatment efficacy and clinical outcomes in pancreatic cancer.

Key words: pancreatic cancer, system biology, multi-targeted therapy