In the era of precision medicine,cancer researchers and oncologists are eagerly searching for more realistic,cost effective,and timely tumor models to aid drug development and precision oncology.Tumor models that can ...In the era of precision medicine,cancer researchers and oncologists are eagerly searching for more realistic,cost effective,and timely tumor models to aid drug development and precision oncology.Tumor models that can faithfully recapitulate the histological and molecular characteristics of various human tumors will be extremely valuable in increasing the successful rate of oncology drug development and discovering the most efficacious treatment regimen for cancer patients.Two‐dimensional(2D)cultured cancer cell lines,genetically engineered mouse tumor(GEMT)models,and patient‐derived tumor xenograft(PDTX)models have been widely used to investigate the biology of various types of cancers and test the efficacy of oncology drug candidates.However,due to either the failure to faithfully recapitulate the complexity of patient tumors in the case of 2D cultured cancer cells,or high cost and untimely for drug screening and testing in the case of GEMT and PDTX,new tumor models are urgently needed.The recently developed patient‐derived tumor organoids(PDTO)offer great potentials in uncovering novel biology of cancer development,accelerating the discovery of oncology drugs,and individualizing the treatment of cancers.In this review,we will summarize the recent progress in utilizing PDTO for oncology drug discovery.In addition,we will discuss the potentials and limitations of the current PDTO tumor models.展开更多
BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasin...BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasing research achievements in this field,a systematic and comprehensive analysis of the research hotspots and future trends is lacking.AIM To address this problem by employing bibliometric tools to explore the publication years,countries/regions,institutions,journals,authors,keywords,and references in this field.METHODS The literature was collected from Web of Science databases.CiteSpace-6.2R4,a widely used bibliometric analysis software package,was used for institutional analysis and reference burst analysis.VOSviewer 1.6.19 was used for journal cocitation analysis,author co-authorship and co-citation analysis.The‘online platform for bibliometric analysis(https://bibliometric.com/app)’was used to assess the total number of publications and the cooperation relationships between countries.Finally,we employed the bibliometric R software package(version R.4.3.1)in R-studio,for a comprehensive scientific analysis of the literature.RESULTS Our analysis included a total of 1466 publications,revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids.The United States(n=393)and Helmholtz Association(n=93)have emerged as the leading countries and institutions,respectively,in this field,with Hans Clevers and Toshiro Sato being the most contributing authors.The most influential journal in this field is Gastroenterology.The most impactful reference is"Long term expansion of epithelial organs from human colon,adenoma,adenocarcinoma,and Barrett's epithelium".Keywords analysis and citation burst analysis indicate that precision medicine,disease modeling,drug development and screening,and regenerative medicine are the most cutting-edge directions.These focal points were further detailed based on the literature.CONCLUSION This bibliometric study offers an objective and quantitative analysis of the research in this field,which can be considered as an important guide for next scientific research.展开更多
Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important...Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important characteristics with their in vivo tumor counterparts.Accordingly,their applications in tumor modeling,drug screening,and precision-targeted treatment are promising.However,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor microenvironment.Recently,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in vitro.Among the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor tissues.In this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model construction.The multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.展开更多
背景:类器官模型可部分还原细胞在体内的组织和分子特性,是一种有良好潜力的临床前模型。与传统精准、再生医学手段相比,类器官能最大程度模拟体内器官,具有组织器官功能;类器官药物敏感性数据较全基因组测序更加准确;能与体外基因编辑...背景:类器官模型可部分还原细胞在体内的组织和分子特性,是一种有良好潜力的临床前模型。与传统精准、再生医学手段相比,类器官能最大程度模拟体内器官,具有组织器官功能;类器官药物敏感性数据较全基因组测序更加准确;能与体外基因编辑技术结合,实现器官水平上的基因改造。目的:总结和分析近10年国内外数据库类器官模型文献的研究热点。方法:计算机检索万方、Web of Science、中国临床试验注册中心、北美临床试验注册中心及SooPAT中国专利数据库与类器官相关的近10年文献,对类器官模型文献的研究热点进行分析总结。结果与结论:①万方数据库检索结果:纳入187篇文献,2019年类器官中文研究呈爆发式增长,其中肠类器官模型研究较多,主要应用领域包括精准医疗、肿瘤研究和个体化医疗;②Web of Science数据库(核心集)检索结果:共纳入2450篇文献,采用Histcite软件分析20篇高被引文章筛选出5条类器官原始经典文献,分别介绍了肠道类器官、多能干细胞衍生的三维大脑类器官、从活检标本和循环肿瘤细胞中长期培养的前列腺癌类器官、含有肾单位的肾类器官及人胃组织三维类器官模型的构建方法,均分别为各领域的开山之作,为类器官后续研究打下了基础;③临床注册信息检索结果:检索到与类器官研究有关的中国临床注册方案13篇,北美临床注册方案23篇,美国类器官临床研究领域更广泛,开展时间更早,但多为队列研究和单臂试验,而中国近年来在类器官临床研究领域已经取得了一些成果,有2个受人瞩目的随机对照试验方案正在进行中;④SooPAT中国专利数据库检索结果:共检索到55项有权专利,主要专利技术涉及3D大脑类器官新型培养方法,高通量3D细胞、类组织及类器官动态培养系统的研发等;⑤上述数据说明,目前研究者已经能够成功构建出多种模拟人体器官功能的类器官体外模型(如肠、脑、肾及各种癌组织),但由于缺乏足够的临床随机对照试验证据,因此临床适用性还有待探讨,而利用癌症患者的肿瘤组织直接培养生成体外肿瘤类器官,分析潜在的药物治疗靶点,进行抗癌药物筛选及开发抗肿瘤新药,将是未来类器官领域主要研究方向。展开更多
文摘In the era of precision medicine,cancer researchers and oncologists are eagerly searching for more realistic,cost effective,and timely tumor models to aid drug development and precision oncology.Tumor models that can faithfully recapitulate the histological and molecular characteristics of various human tumors will be extremely valuable in increasing the successful rate of oncology drug development and discovering the most efficacious treatment regimen for cancer patients.Two‐dimensional(2D)cultured cancer cell lines,genetically engineered mouse tumor(GEMT)models,and patient‐derived tumor xenograft(PDTX)models have been widely used to investigate the biology of various types of cancers and test the efficacy of oncology drug candidates.However,due to either the failure to faithfully recapitulate the complexity of patient tumors in the case of 2D cultured cancer cells,or high cost and untimely for drug screening and testing in the case of GEMT and PDTX,new tumor models are urgently needed.The recently developed patient‐derived tumor organoids(PDTO)offer great potentials in uncovering novel biology of cancer development,accelerating the discovery of oncology drugs,and individualizing the treatment of cancers.In this review,we will summarize the recent progress in utilizing PDTO for oncology drug discovery.In addition,we will discuss the potentials and limitations of the current PDTO tumor models.
基金Supported by The Science and Technology Program of Gansu Province,No.23JRRA1015.
文摘BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasing research achievements in this field,a systematic and comprehensive analysis of the research hotspots and future trends is lacking.AIM To address this problem by employing bibliometric tools to explore the publication years,countries/regions,institutions,journals,authors,keywords,and references in this field.METHODS The literature was collected from Web of Science databases.CiteSpace-6.2R4,a widely used bibliometric analysis software package,was used for institutional analysis and reference burst analysis.VOSviewer 1.6.19 was used for journal cocitation analysis,author co-authorship and co-citation analysis.The‘online platform for bibliometric analysis(https://bibliometric.com/app)’was used to assess the total number of publications and the cooperation relationships between countries.Finally,we employed the bibliometric R software package(version R.4.3.1)in R-studio,for a comprehensive scientific analysis of the literature.RESULTS Our analysis included a total of 1466 publications,revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids.The United States(n=393)and Helmholtz Association(n=93)have emerged as the leading countries and institutions,respectively,in this field,with Hans Clevers and Toshiro Sato being the most contributing authors.The most influential journal in this field is Gastroenterology.The most impactful reference is"Long term expansion of epithelial organs from human colon,adenoma,adenocarcinoma,and Barrett's epithelium".Keywords analysis and citation burst analysis indicate that precision medicine,disease modeling,drug development and screening,and regenerative medicine are the most cutting-edge directions.These focal points were further detailed based on the literature.CONCLUSION This bibliometric study offers an objective and quantitative analysis of the research in this field,which can be considered as an important guide for next scientific research.
基金The authors appreciated the financial support from the National Key R&D Program of China(No.2018YFA0703000)the National Natural Science Foundation of China(No.82072412)+2 种基金the Translation Medicine National Key Science and Technology Infrastructure(Shanghai)Open Project(No.TMSK-2020-118)the Lingang Laboratory“Seeking Outstanding Youth Program”Open Project(No.LG-QS-202206-04)the Shanghai Municipal Natural Science Foundation(No.19ZR1429100).
文摘Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important characteristics with their in vivo tumor counterparts.Accordingly,their applications in tumor modeling,drug screening,and precision-targeted treatment are promising.However,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor microenvironment.Recently,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in vitro.Among the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor tissues.In this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model construction.The multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.
文摘背景:类器官模型可部分还原细胞在体内的组织和分子特性,是一种有良好潜力的临床前模型。与传统精准、再生医学手段相比,类器官能最大程度模拟体内器官,具有组织器官功能;类器官药物敏感性数据较全基因组测序更加准确;能与体外基因编辑技术结合,实现器官水平上的基因改造。目的:总结和分析近10年国内外数据库类器官模型文献的研究热点。方法:计算机检索万方、Web of Science、中国临床试验注册中心、北美临床试验注册中心及SooPAT中国专利数据库与类器官相关的近10年文献,对类器官模型文献的研究热点进行分析总结。结果与结论:①万方数据库检索结果:纳入187篇文献,2019年类器官中文研究呈爆发式增长,其中肠类器官模型研究较多,主要应用领域包括精准医疗、肿瘤研究和个体化医疗;②Web of Science数据库(核心集)检索结果:共纳入2450篇文献,采用Histcite软件分析20篇高被引文章筛选出5条类器官原始经典文献,分别介绍了肠道类器官、多能干细胞衍生的三维大脑类器官、从活检标本和循环肿瘤细胞中长期培养的前列腺癌类器官、含有肾单位的肾类器官及人胃组织三维类器官模型的构建方法,均分别为各领域的开山之作,为类器官后续研究打下了基础;③临床注册信息检索结果:检索到与类器官研究有关的中国临床注册方案13篇,北美临床注册方案23篇,美国类器官临床研究领域更广泛,开展时间更早,但多为队列研究和单臂试验,而中国近年来在类器官临床研究领域已经取得了一些成果,有2个受人瞩目的随机对照试验方案正在进行中;④SooPAT中国专利数据库检索结果:共检索到55项有权专利,主要专利技术涉及3D大脑类器官新型培养方法,高通量3D细胞、类组织及类器官动态培养系统的研发等;⑤上述数据说明,目前研究者已经能够成功构建出多种模拟人体器官功能的类器官体外模型(如肠、脑、肾及各种癌组织),但由于缺乏足够的临床随机对照试验证据,因此临床适用性还有待探讨,而利用癌症患者的肿瘤组织直接培养生成体外肿瘤类器官,分析潜在的药物治疗靶点,进行抗癌药物筛选及开发抗肿瘤新药,将是未来类器官领域主要研究方向。
