摘要
目的总结类器官模型在胰腺癌中的临床应用情况及未来应用前景。方法检索近几年来国内外关于类器官模型在胰腺癌中的相关研究的文献并进行综述。结果近年来,胰腺癌类器官模型的构建主要采用手术切除的癌组织、细针穿刺抽吸活检获得的癌组织或人多能干细胞衍生的上皮细胞构建;根据胰腺癌类器官保留了原发肿瘤的组织学、结构异质性等特点来进行胰腺癌生物学标志物的筛选,如细胞外囊泡中的微小RNA、glypican-1、膜联蛋白A6以及蛋白质生物学标志物细胞角蛋白7和20、细胞肿瘤抗原p53、Claudin-4、糖类抗原19-9等。根据类器官模型能够维持原发肿瘤组织特性的研究结果以及胰腺癌类器官药物敏感性数据与胰腺癌患者的临床结果之间存在高度相关性的结果提示,未来利用胰腺癌类器官进行的药物敏感性的数据可避免无效化学药物治疗,以提高治疗应答率和减轻化学药物毒性,可为胰腺癌患者合理选择个体化治疗方案。结论类器官模型用于胰腺癌生物学标志物筛选和类器官模型与胰腺癌个体化治疗及药物敏感性测试方面有较多研究成果,它可在体外模拟胰腺癌发病和进展的复杂病理生理学特征,并保留了原发肿瘤细胞的生理特性和基因表型,有望成为发现胰腺癌生物学标志物、测试药物敏感性及制定个体化胰腺癌治疗方案的新型平台,可进一步促进胰腺癌的研究进展。
Objective To summarize the clinical application and future application prospects of organoid model in pancreatic cancer.Method The domestic and foreign literature related on the application of organoid model in pancreatic cancer was reviewed.Results In recent years,the organoid model of pancreatic cancer was constructed mainly using patient-derived tissues,fine-needle aspiration samples,and human pluripotent stem cells.The biomarkers of pancreatic cancer were screened according to the histological and structural heterogeneities of the primary tumor retained in organoid model,such as microRNA,glypican-1,annexin A6 and protein biomarkers cytokeratin 7 and 20,cell tumor antigen p53,Claudin-4,carbohydrate antigen 19-9,etc.in the extracellular vesicles.The results of organoid model could maintain the original tumor characteristics and the higher correlation between the organoid model drug sensitivity data and the clinical results of pancreatic cancer patients suggested that,the drug sensitivity data of organoid model could be used to avoid ineffective chemotherapy,so as to improve the treatment response rate and reduce the toxicity of chemical drug treatment,and reasonably select individualized treatment plans for pancreatic cancer patients in future.Conclusions Organoid model has many research in screening biomarkers of pancreatic cancer,individualized drug screening,and drug sensitivity test.It can simulate the complex pathophysiological characteristics of pancreatic cancer in vitro,and retain the physiological characteristics and gene phenotype of original tumor cells.It is expected to become a new platform for selecting biomarkers of pancreatic cancer,testing drug sensitivity,and formulating individualized treatment methods for pancreatic cancer,which might further accelerate the research progress of pancreatic cancer.
作者
彭磊
朱克祥
PENG Lei;ZHU Kexiang(The First Clinical College of Medicine,Lanzhou University,Lanzhou 730000,P.R.China;Department of General Surgery,The First Hospital of Lanzhou University,Lanzhou 730000,China)
出处
《中国普外基础与临床杂志》
CAS
2023年第7期863-869,共7页
Chinese Journal of Bases and Clinics In General Surgery
基金
国家自然科学基金资助项目(项目编号:81960516)。
关键词
胰腺癌
类器官
生物标志物
个体化药物筛选
药物敏感性测试
pancreatic cancer
organoids
biomarkers
personalized drug screening
drug sensitivity testing