Establishment of organoid models for pancreatic ductal adenocarcinoma and screening of individualized therapy strategy  

作　　者：Miaomiao Gong Han Meng Dengxu Tan Peng Li Jing Qin Qingling An Changhong Shi Jiaze An 

机构地区：[1]Division of Cancer Biology,Laboratory Animal Center,Fourth Military Medical University,Xi'an,China [2]School of Basic Medical Sciences,Medical College of Yan'an University,Yanan,China [3]Animal Experiment Center,Guangzhou University of Chinese Medicine,Guangzhou,China [4]Department of Hepatobiliary and Pancreaticosplenic Surgery,Xijing Hospital,Fourth Military Medical University,Xi'an,China

出　　处：《Animal Models and Experimental Medicine》2023年第5期409-418,共10页动物模型与实验医学（英文）

基　　金：Laboratory Animal Foundation Program,Grant/Award Number:SYDW_KY 2021-14;National Natural Science Foundation of China,Grant/Award Number:32070532 and 32270566;Promotion Plan of the Air Force Medical University,Grant/Award Number:2020SWAQ11;the Ethics Committee of Xijing Hospital of FMMU(ethics approval number:KY20203128-1).

摘　　要：Background:Patients with pancreatic ductal adenocarcinoma(PDAC)who undergo surgical resection and receive effective chemotherapy have the best chance for longterm survival.Unfortunately,because of the heterogeneity of pancreatic cancer,it is difficult to find a personalized treatment strategy for patients.Organoids are ideal preclinical models for personalized medicine.Therefore,we explore the cultivation conditions and construction methods of PDAC organoid models to screen the individualized therapy strategy.Methods:Fresh PDAC tissues from surgical resection were collected and digested with digestive enzymes;then the tumor cells were embedded in Matrigel with a suitable medium to establish the PDAC organoid models.The genetic stability of the organoids was analyzed using whole exon sequencing;hematoxylin and eosin staining and immunohistochemistry of organoids were performed to analyze their consistency with the pathological morphology of the patient's tumor tissue;After 2 days of organoid culture,we selected four commonly used clinical chemotherapy drugs for single or combined treatment to analyze drug sensitivity.Results:Two cases of PDAC organoid models were successfully established,and the results of their pathological characteristics and exome sequencing were consistent with those of the patient's tumor tissue.Both PDAC organoids showed more sensitivity to gemcitabine and cisplatin,and the combined treatment was more effective than monotherapy.Conclusion:Both organoids better retained the pathological characteristics,genomic stability,and heterogeneity with the original tumor.Individual PDAC organoids exhibited different sensitivities to the same drugs.Thus,this study provided ideal experimental models for screening individualized therapy strategy for patients with PDAC.

关 键 词：3D CULTURE individualized therapy organoid PANCREATIC DUCTAL ADENOCARCINOMA 

分 类 号：R735.9[医药卫生—肿瘤]