摘要
近年来,胰腺腺鳞癌(pancreatic adenosquamous carcinoma,PASC)因其罕见性与高度恶性逐渐受到关注。作为一种同时包含腺癌与鳞癌成分的特殊亚型,其临床预后显著差于胰腺导管腺癌,中位生存期仅6个月。该文综述PASC的主要分子机制,包括TP53/NOTCH通路失活、具有转录调控功能的ΔNp63和转录因子SRY-box转录因子2(SRY-box transcription factor 2,SOX2)的上调,以及Zeste增强子同源物2(enhancer of zeste homolog 2,EZH2)介导的表观遗传重塑,探讨其在谱系转分化和肿瘤可塑性中的作用。同时,结合高通量测序与单细胞多组学的研究,介绍PASC免疫微环境的抑制性特征及其对治疗反应的影响。文章还分析了当前研究中存在的不足,如病例数量有限、临床循证证据缺乏、机制研究与转化脱节等,最后展望通过多中心临床研究和分子分型,探索表观遗传抑制剂联合免疫治疗等新策略,以期改善患者的诊疗结局。
In recent years,pancreatic adenosquamous carcinoma(PASC)has drawn growing attention owing to its rarity and highly aggressive characteristics.As a distinct subtype defined by the co-existence of adenocarcinoma and squamous carcinoma components,PASC is linked to substantially worse prognoses compared to pancreatic ductal adenocarcinoma,with a median survival period of merely six months.This review outlines the key molecular mechanisms underlying PASC,such as the inactivation of the TP53/NOTCH pathways,the up-regulation of the transcriptional regulatorΔNp63 and the transcription factor SRY-box transcription factor 2(SOX2),along with enhancer of zeste homolog 2(EZH2)-mediated epigenetic remodeling,and deliberates on their functions in lineage transdifferentiation and tumor plasticity.We further synthesize findings from high-throughput sequencing and single-cell multi-omics studies to depict the immunosuppressive traits of the PASC tumor microenvironment and their implications for therapeutic resistance.Current challenges are also addressed,including the scarce number of reported cases,the absence of high-level clinical evidence,and the disparity between mechanistic studies and clinical translation.Finally,we suggest that future research ought to concentrate on establishing multicenter clinical cohorts and molecular stratification approaches,and on exploring novel therapeutic strategies like combining epigenetic inhibitors with immunotherapy,with the ultimate aim of enhancing patient outcomes.
作者
安建虹
宋美慧
黄长文
AN Jianhong;SONG Meihui;HUANG Changwen(Department of General Surgery,Affiliated Qingyuan Hospital of Guangzhou Medical University(Qingyuan People's Hospital),Qingyuan 511500,Guangdong,China;Department of Gastroenterology,Affiliated Qingyuan Hospital of Guangzhou Medical Universit(Qingyuan People's Hospital),Qingyuan 511500,Guangdong,China)
出处
《实用医学杂志》
北大核心
2026年第2期169-175,共7页
The Journal of Practical Medicine
基金
国家自然科学基金项目(编号:82203351)
广东省基础与应用基础研究基金项目(编号:2023A1515111002)
广州医科大学附属清远医院(清远市人民医院)科研项目(编号:11018)。
关键词
胰腺腺鳞癌
组织学特征
分子机制
肿瘤微环境
治疗前景
pancreatic adenosquamous carcinoma
histological features
molecular mechanisms
tumor microenvironment
therapeutic prospects
