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patient-derived organoids (PDOs) and PDO-derived xenografts (PDOXs): New opportunities in establishing faithful pre-clinical cancer models

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Journal of the National Cancer Center 2022年第4期2卷 263-276页

作者： Ergang Wang Kun Xiang Yun Zhang Xiao-Fan Wang Department of Pharmacology and Cancer Biology Duke UniversityDurhamUnited States State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

One of the major bottlenecks in advancing basic cancer research and developing novel cancer therapies is the lack of in vitro pre-clinical models that faithfully recapitulate tumor properties in the *** cultures of cancer cell lines usually lose the heterogeneity of the parental tumors,while patient-derived xenograft(PDX)suffers from its time-and resource-intensive *** emergence of organoid culture system and its application in cancer research provides a unique opportunity to develop novel in vitro cancer pre-clinical *** we review the recent advances in utilizing organoids culture system and other related three-dimensional culture systems in studying cancer biology,performing drug screening,and developing cancer *** particular,we discuss the advantages of applying xenograft initiated from patient-derived organoids(PDOs)as a faithful cancer pre-clinical model in basic cancer research and precision medicine.

关键词： patient-derived organoid patient-derived xenograft PDO-derived xenograft

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patient-derived organoids potentiate precision medicine in advanced clear cell renal cell carcinoma

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Precision Clinical Medicine 2022年第4期5卷 215-221页

作者： Yizheng Xue Bingran Wang Yiying Tao Jun Xia Kedi Yuan Junhua Zheng Wei Zhai Wei Xue Department of Urology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Ottawa-Shanghai Joint School of Medicine Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Pathology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China

To investigate the role of patient-derived organoid(PDO)model in the precision medicine of advanced clear cell renal cell carcinoma(ccRCC),we retrospectively analyzed the clinical data of seven cases of ccRCC diagnosed by operation and pathology in Renji Hospital from September 2021 to September *** seven patients were diagnosed with advanced ccRCC with or without remote *** and radical nephrectomy was performed *** predict the response to immunotherapy and provide personalized medicine recommendation,a PDO model based on air-liquid interface system was established from the surgical resected tumor and subsequent drug screening was *** and eosin(H&E)staining and immunohistochemistry revealed that the PDO recapitulated the histological feature of parent *** staining identified that CD3^(+)T cells,SMA^(+)cancer associated fibroblasts,and CD31^(+)endothelial cells were preserved in PDO *** activated cell sorter(FACS)revealed an evidently increased ratio of CD8^(+)/CD4^(+)T cells and apoptotic tumor cells in PDO treated with toripalimab than those treated with *** results showed that toripalimab is able to rescue the excessive death of CD8^(+)T cells by critically reversing the immune exhaustion state of ccRCC in PDO *** research validated that PDO is a promising and faithful preclinical model for prediction of immunotherapy response in patients with ccRCC.

关键词： patient-derived organoid air-liquid interface tumor microenvironment immunotherapy renal cell carcinoma

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Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

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Cancer Communications 2024年第1期44卷 101-126页

作者： Monika Raab Izabela Kostova Samuel Peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt Department of Gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational Genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany German Cancer Consortium(DKTK) EssenGermany German Cancer Research Center(DKFZ) HeidelbergGermany Histology and Embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany German Cancer Consortium(DKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human *** various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of *** intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 *** this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in ***:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector ***,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal *** alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way *** vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse ***:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based *** introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell *** analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA *** p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baselin

关键词： apoptosis cell cycle chromosomal instability HGSOC metastatic intraperitoneal mouse model HGSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

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