2024年胰腺癌研究及诊疗新进展

王婷; 秦毅; 徐晓武; 虞先濬

doi:10.19401/j.cnki.1007-3639.2025.01.001

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2024年胰腺癌研究及诊疗新进展

专家述评 | 更新时间：2025-12-31

- 2024年胰腺癌研究及诊疗新进展
- New advances in basic research, clinical diagnosis and treatment of pancreatic cancer in 2024
- 中国癌症杂志 2025年35卷第1期页码：1-11
- 作者机构：
  
  复旦大学附属肿瘤医院胰腺外科，复旦大学上海医学院肿瘤学系，上海市胰腺肿瘤研究所，上海市胰腺肿瘤精准诊疗重点实验室，复旦大学胰腺肿瘤研究所，上海 200032
- 作者简介：
  
  [ "王婷（ORCID: 0000-0002-8831-6215），博士。" ]
  [ "虞先濬，主任医师，二级教授，博士研究生导师，复旦大学附属肿瘤医院院长，上海市胰腺肿瘤研究所所长，复旦大学胰腺肿瘤研究所所长。国家杰出青年科学基金获得者，国家科技部“中青年科技创新领军人才”，国家百千万人才工程“有突出贡献中青年专家”。享受国务院政府特殊津贴，全国五一劳动奖章获得者，上海市科技精英，上海工匠，上海市领军人才，上海市优秀学术带头人。担任中国抗癌协会胰腺癌专业委员会主任委员，中国胰腺癌多学科协作组组长，中华医学会外科学分会胰腺外科学组委员，中国医师协会胰腺病学专业委员会常务委员，中国临床肿瘤学会胰腺癌专家委员会常务委员，美国外科医师学院Fellow（FACS）等职务。主持国家杰出青年科学基金1项，国家自然科学基金区域合作重点项目1项，国家自然科学基金中德合作项目1项，国家自然科学基金面上项目3项，省部级项目12项。以通信作者在Journal of Clinical Oncology、Cell Research、GUT、Annals of Surgery、Autophagy、Clinical Cancer Research、Cancer Research等国际权威SCI收录期刊上发表论文250余篇。获上海市科技进步一等奖、中国抗癌协会科技奖一等奖、上海医学科技奖一等奖、上海市职工优秀创新成果奖一等奖。" ]
- 基金信息：
  
  国家自然科学基金(U21A20374);国家自然科学基金(82373006);国家自然科学基金(82172948);国家自然科学基金(82141129);国家自然科学基金(82173281);上海市科学技术重大项目(21JC1401500)
- DOI：10.19401/j.cnki.1007-3639.2025.01.001
  中图分类号： R735.9
- 收稿：2024-12-31，
  
  修回：2025-01-21，
  
  纸质出版：2025-01-30
- 稿件说明：
移动端阅览
王婷, 秦毅, 徐晓武, 等. 2024年胰腺癌研究及诊疗新进展[J]. 中国癌症杂志, 2025,35(1):1-11.

Ting WANG, Yi QIN, Xiaowu XU, et al. New advances in basic research, clinical diagnosis and treatment of pancreatic cancer in 2024[J]. China Oncology, 2025, 35(1): 1-11.
王婷, 秦毅, 徐晓武, 等. 2024年胰腺癌研究及诊疗新进展[J]. 中国癌症杂志, 2025,35(1):1-11. DOI： 10.19401/j.cnki.1007-3639.2025.01.001.

Ting WANG, Yi QIN, Xiaowu XU, et al. New advances in basic research, clinical diagnosis and treatment of pancreatic cancer in 2024[J]. China Oncology, 2025, 35(1): 1-11. DOI： 10.19401/j.cnki.1007-3639.2025.01.001.

摘要

胰腺癌是一种恶性程度极高的恶性肿瘤，其发病率自2000年以来呈缓慢增长趋势。尽管诊疗水平的提升促使胰腺癌患者的5年生存率相较于50年前有了一定提高，但仍是预后不容乐观的恶性肿瘤之一。步入2024年，胰腺癌早期筛查策略、疾病机制探索、临床诊疗方案等研究领域取得了诸多进展，并显示出良好的临床应用前景。早期筛查方面，人工智能（artificial intelligence，AI）技术赋能胰腺癌早诊、早筛，使临床诊疗踏上新台阶；此外，液体活检等技术的准确率提升，为胰腺癌早筛提供了新方向。疾病发病机制研究方面，3D基因组映射技术揭示了胰腺导管上皮内瘤变（pancreatic intraepithelial neoplasm，PanIN）的多克隆起源和遗传异质性。基础研究方面，模拟胰腺癌独特结构特征的分支器官模拟系统为胰腺癌体外研究提供了新模型；肿瘤重要代谢物乳酸将胰腺癌代谢微环境与表观遗传学改变联系在一起，揭示了潜在治疗靶点；组蛋白H3K36三甲基转移酶SETD2缺陷导致胰腺癌内源性表观遗传失调，并促进线粒体氧化磷酸化（oxidative phosphorylation，OXPHOS）和肿瘤进展；基质细胞与癌细胞间信号分子血小板衍生生长因子受体（platelet-derived growth factor receptor，PDGFR）轴形成双向分泌回路，或能成为治疗新靶点；嵌合抗原受体巨噬细胞（chimeric antigen receptor macrophage，CAR-M）靶向c-MET的疗法展现出与化疗药物协同增效的潜力；胰腺癌微环境中的巨噬细胞通过CCL5/TRAF6/核因子-κB（nuclear factor-κB，NF-κB）通路促进胰腺癌恶病质进展，表明巨噬细胞有望成为预测及干预胰腺癌恶病质发生、发展的有效靶点。诊疗方面，新辅助化疗后手术可改善可切除与交界可切除患者的总生存（overall survival，OS），但仍需进一步优化新辅助化疗方案；首个临床有效的KRAS

G12D

靶向药物已见报道，广谱

KRAS

突变体抑制剂研究不断涌现；通过糖酵解相关评分（glycolysis-related scores，GRS）进行患者分层能够进一步指导治疗方案选择；“智能外泌体”（Exo

Smart

）通过增强细胞摄取能力协助提高化疗效果；免疫治疗联合化疗临床试验的实施，有望协同提高胰腺癌疗效；派安普利单抗和安罗替尼联合白蛋白结合型紫杉醇/吉西他滨（PAAG）在一线转移性胰腺癌（metastatic pancreatic cancer，mPC）患者中显示出较好的疗效和安全性；靶向

KRAS

突变编码新抗原的癌症疫苗ELI-002 2P能够诱导抗肿瘤免疫反应；溶瘤腺病毒疗法能够协同化疗

药物提高晚期胰腺导管腺癌患者的疗效。本文就2024年度胰腺癌基础研究和诊疗领域的最新重大进展进行综述。

Abstract

Pancreatic cancer is a highly malignant tumor

and its incidence rate has been slowly increasing since 2000. Although the improvement of diagnosis and treatment has led to an increase in the five-year survival rate of pancreatic cancer compared to 50 years ago

it remains one of the discouraging tumor diseases regarding its prognosis. In 2024

many achievements were made in the research of early screening

disease mechanism

clinical diagnosis and treatment of pancreatic cancer

showing a good prospect for clinical application. In early screening

artificial intelligence (AI) technology has empowered early diagnosis and screening of pancreatic cancer

pushing clinical diagnosis and treatment to a new level. Additionally

improvements in the accuracy of technologies such as liquid biopsy have provided new directions for early screening of pancreatic cancer. In terms of research on disease pathogenesis

3D genome mapping technology has revealed the polyclonal origin and genetic heterogeneity of pancreatic intraepithelial neoplasm (PanIN). In basic research

a branched organ simulation system that mimics the unique structural characteristics of pancreatic cancer provides a new model for

in vitro

studies of pancreatic cancer. Lactate

an important tumor metabolite

links the metabolic microenvironment of pancreatic cancer with epigenetic changes

revealing potential therapeutic targets. Defects in the histone H3K36 trimethyltransferase SETD2 contribute to endogenous epigenetic dysregulation in pancreatic cancer and promote mitochondrial oxidative phosphorylation (OXPHOS) and tumor progression. The platelet-derived growth factor receptor (PDGFR) axis

which facilitates communication between stromal cells and cancer cells

forms a bidirectional secretory circuit and may become a new therapeutic target. Chimeric antigen receptor macrophage (CAR-M) therapy targeting

the tyrosine kinase receptor c-MET demonstrates potential for synergistic enhancement with chemotherapy drugs. Macrophages in the pancreatic cancer microenvironment promote the development of pancreatic cancer cachexia through the CCL5/TRAF6/nuclear factor-κB (NF-κB) pathway

suggesting that macrophages could be an effective target for predicting and intervening in the development of pancreatic cancer cachexia. In terms of advancements in diagnosis and treatment

surgery following neoadjuvant chemotherapy can improve overall survival (OS) in resectable and borderline resectable patients

but further optimization of neoadjuvant chemotherapy protocols is needed. The first clinically effective KRAS

G12D

-targeted drug has been reported

and research on inhibitors of a wide range of KRAS mutants is continually emerging. Patient stratification based on glycolysis-related scores (GRS) can further guide the selection of treatment protocols. “Intelligent exosomes” (Exo

Smart

) enhance cellular uptake capacity to assist in improving chemotherapy efficacy. The implementation of clinical trials combining immunotherapy with chemotherapy is expected to synergistically improve the efficacy of pancreatic cancer treatment. Pembrolizumab and anlotinib combined with albumin-bound paclitaxel/gemcitabine (PAAG) have shown great efficacy and safety in first-line treatment of metastatic pancreatic cancer (mPC) patients. The cancer vaccine ELI-002 2P

which targets

KRAS

mutation-encoded neoantigens

can induce an antitumor immune response. Oncolytic adenovirus therapy can synergistically improve the efficacy of treatment in advanced pancreatic ductal adenocarcinoma patients when combined with chemotherapy. This article reviewed the latest major progress in the field of basic research and diagnosis and treatment of pancreatic cancer in 2024.

关键词

Keywords

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