DOI: 10.1002/ame2.12352
Establishment of organoid models for pancreatic ductal adenocarcinoma and screening of individualized therapy strategy
Miaomiao Gong1
Han Meng2
Dengxu Tan2
Peng Li3
Jing Qin2
Qingling An2
Changhong Shi2
Jiaze An4
1.Division of Cancer Biology,Laboratory Animal Center,Fourth Military Medical University,Xi'an,China;School of Basic Medical Sciences,Medical College of Yan'an University,Yanan,China2.Division of Cancer Biology,Laboratory Animal Center,Fourth Military Medical University,Xi'an,China3.Division of Cancer Biology,Laboratory Animal Center,Fourth Military Medical University,Xi'an,China;Animal Experiment Center,Guangzhou University of Chinese Medicine,Guangzhou,China4.Department of Hepatobiliary and Pancreaticosplenic Surgery,Xijing Hospital,Fourth Military Medical University,Xi'an,China
摘要：Background:Patients with pancreatic ductal adenocarcinoma(PDAC)who undergo surgical resection and receive effective chemotherapy have the best chance for long-term 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 indi-vidualized 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 suit-able medium to establish the PDAC organoid models.The genetic stability of the or-ganoids 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 orga-noid 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 re-sults of their pathological characteristics and exome sequencing were consistent with those of the patient's tumor tissue.Both PDAC organoids showed more sensitivity to gem-citabine 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 exhib-ited different sensitivities to the same drugs.Thus,this study provided ideal experi-mental models for screening individualized therapy strategy for patients with PDAC.
机标关键词：strategyscreeningmodelsadenocarcinomaductalestablishmentindividualizedorganoid
论文发表日期：2023-10-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 409-418 )
英文信息