中国实用外科杂志

中国实用外科杂志

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胰腺癌靶向及免疫治疗——从“无为”到“可为”再到“有为”

杨尹默1，许静涌2   

  1. 1北京大学第一医院肝胆胰外科，北京100028；2北京医院普外科，北京100730
  • 出版日期:2025-06-01

  • Online:2025-06-01

摘要： 胰腺癌是恶性程度最高的消化道肿瘤之一，病人总体5年生存率仅为13%。近年来，随着肿瘤分子生物学研究的深入，基于分子分型及靶向干预的个体化治疗策略成为发展方向，逐步从“异病同治”向“同病异治”转变。同时，多学科协作模式与病人全生命周期管理的广泛实践进一步优化了综合治疗体系，既防止治疗不足，又力求避免过度治疗。然而，胰腺癌的高度异质性、关键驱动基因靶向干预手段匮乏、肿瘤细胞原发及获得性耐药、免疫抑制性微环境等生物学特征，仍严重制约精准分子分型及个体化治疗的发展，导致病人预后未显著改善，临床诊治仍然面临巨大挑战。已有研究结果表明，不同分子分型（经典型、原浆型、准间质型、鳞状型等）与临床表型之间存在关联；液体活检技术可用于辅助早期诊断及动态监测。靶向治疗方面聚焦于KRAS及耐药机制的研究；免疫治疗需突破低免疫原性及免疫抑制性肿瘤微环境的限制，多项联合治疗策略正在临床探索。人工智能（AI）与大数据有望优化影像诊断、分子分型和术中导航等环节。未来需加强多学科协作，将分子分型、靶向和免疫治疗以及AI技术有机结合，以实现胰腺癌精准化综合治疗。

关键词: 胰腺癌, 分子分型, 液体活检, 靶向治疗, 免疫治疗, 人工智能, 多学科协作, 个体化精准治疗

Abstract: Pancreatic cancer is among the most lethal malignancies of the digestive system, with an overall 5-year survival rate of only 13%. In recent years, advances in tumor molecular biology have shifted therapeutic strategies from a “one-size-fits-all” approach to molecular subtype-based, targeted, and personalized therapies. Concurrently, the widespread implementation of multidisciplinary team (MDT) collaboration and full-cycle patient management has optimized the comprehensive treatment paradigm, aiming to balance undertreatment and overtreatment. However, the high heterogeneity of pancreatic cancer, limited availability of targeted approaches for key driver genes, intrinsic and acquired resistance mechanisms, and the immunosuppressive tumor microenvironment continue to significantly hinder the advancement of precision molecular classification and individualized treatment, leading to no substantial improvement in patient prognosis to date and enormous challenges in clinical diagnosis and treatment. Current research indicates correlations between molecular subtypes (including classical, basal-like, quasi-mesenchymal, and squamous) and clinical phenotypes. Liquid biopsy technologies—such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes—are being explored for early diagnosis and real-time disease monitoring. In targeted therapy, research is centered on KRAS and resistance mechanisms. Immunotherapy must overcome the challenges of low immunogenicity and an immunosuppressive tumor microenvironment, with various combination strategies undergoing clinical investigation. Artificial intelligence (AI) and big data are expected to enhance diagnostic imaging, molecular subtyping, and intraoperative navigation. Future directions should focus on strengthening interdisciplinary collaboration and integrating molecular classification, targeted and immunotherapeutic strategies, and AI technology to realize precision, comprehensive treatment for pancreatic cancer.

Key words: pancreatic cancer, molecular subtyping, liquid biopsy, targeted therapy, immunotherapy, artificial intelligence, multidisciplinary collaboration, personalized precision therapy