Next-generation cancer organoids.

文献信息

DOI	10.1038/s41563-021-01057-5
PMID	34385685
期刊	Nature materials
影响因子	38.5
JCR 分区	Q1
发表年份	2022
被引次数	208
关键词	癌症类器官, 个性化医学, 生物异质性, 标准化, 转化研究
文献类型	Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN	1476-1122
页码	143-159
期号	21(2)
作者	Bauer L LeSavage, Riley A Suhar, Nicolas Broguiere, Matthias P Lutolf, Sarah C Heilshorn

一句话小结

本研究探讨了患者特异性肿瘤的器官类模型在理解癌症异质性及个性化医疗中的重要性，指出目前技术的不可重现性主要源于多种非标准化因素。通过消除这些技术变异，未来可望建立更为可靠的培养平台，从而加速对患者护理的转化研究。

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癌症类器官 · 个性化医学 · 生物异质性 · 标准化 · 转化研究

摘要

患者特异性肿瘤的器官类模型正在革新我们对癌症异质性及其对个性化医疗影响的理解。这些进展在一定程度上归因于器官类模型能够在体外稳定地保留母体肿瘤的遗传、蛋白质组学、形态学和药物特征，同时也提供了前所未有的基因组和环境操控。尽管近年来在器官类培养协议方面有所创新，但目前的癌症器官类培养技术本质上仍然是无控制且无法重现的，这主要是由于多种非标准化的因素，包括癌症组织来源及后续加工、培养基配方以及动物来源的三维基质。鉴于癌症器官类有潜力准确重现与患者特异性癌症相关的肿瘤内外生物异质性，消除癌症器官类培养中不理想的技术变异是建立可重现的平台的必要条件，从而加速可转化的患者护理见解的形成。本文将描述当前的挑战以及在标准化下一代癌症器官类系统方面的最新多学科进展和机遇。

英文摘要

Organotypic models of patient-specific tumours are revolutionizing our understanding of cancer heterogeneity and its implications for personalized medicine. These advancements are, in part, attributed to the ability of organoid models to stably preserve genetic, proteomic, morphological and pharmacotypic features of the parent tumour in vitro, while also offering unprecedented genomic and environmental manipulation. Despite recent innovations in organoid protocols, current techniques for cancer organoid culture are inherently uncontrolled and irreproducible, owing to several non-standardized facets including cancer tissue sources and subsequent processing, medium formulations, and animal-derived three-dimensional matrices. Given the potential for cancer organoids to accurately recapitulate the intra- and intertumoral biological heterogeneity associated with patient-specific cancers, eliminating the undesirable technical variability accompanying cancer organoid culture is necessary to establish reproducible platforms that accelerate translatable insights into patient care. Here we describe the current challenges and recent multidisciplinary advancements and opportunities for standardizing next-generation cancer organoid systems.

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主要研究问题

核心洞察

研究背景和目的

癌症的异质性是个体化治疗的重大障碍，患者的肿瘤表型各异，且在疾病进展和临床治疗中动态变化。癌症类器官（organoids）作为一种新兴的模型，能够在体外稳定地保留肿瘤的遗传、蛋白质组、形态学和药物特征。本文旨在探讨当前癌症类器官培养的技术挑战，强调标准化下一代癌症类器官系统的重要性，以促进个体化医疗的发展。

主要方法/材料/实验设计

本研究综述了癌症类器官的生成方法、技术创新及其在标准化方面的进展。类器官被定义为来自患者特定组织样本的三维自组织细胞集合，能够模拟原肿瘤的关键特征。研究采用了多学科的技术，涉及以下关键步骤：

关键结果和发现

异质性建模：癌症类器官能够再现患者特定肿瘤的基因组和表型多样性，并模拟肿瘤微环境（TME）的异质性。
药物反应预测：通过类器官平台，研究人员能够高效地测试化疗、免疫疗法和放疗等治疗手段的效果，显示出类器官在个体化治疗中的潜力。
标准化问题：当前的类器官培养方法存在技术变异性，包括组织来源、培养基配方和三维基质的使用不一致，影响了结果的可重复性。

主要结论/意义/创新性

类器官技术的标准化对于理解肿瘤的生物学异质性和提高治疗预测能力至关重要。研究表明，未来的类器官生成方法应关注于降低技术变异性，确保实验结果的可重复性，从而推动精准医学的发展。

研究局限性和未来方向

局限性：类器官的生成效率在某些癌症亚型中较低，且目前大多数研究集中于上皮肿瘤，非上皮癌症的类器官研究仍较为缺乏。
未来方向：未来研究应关注开发可重复的类器官生成技术，利用微流控和生物材料工程技术提升肿瘤微环境的模拟，探索不同细胞类型在类器官中的相互作用，以及其对肿瘤生物学和药物反应的影响。

通过上述研究，本文为癌症类器官的标准化和临床应用提供了重要的见解和未来研究方向。

参考文献

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Guided self-organization and cortical plate formation in human brain organoids. - Madeline A Lancaster;Nina S Corsini;Simone Wolfinger;E Hilary Gustafson;Alex W Phillips;Thomas R Burkard;Tomoki Otani;Frederick J Livesey;Juergen A Knoblich - Nature biotechnology (2017)
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The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. - Paraic A Kenny;Genee Y Lee;Connie A Myers;Richard M Neve;Jeremy R Semeiks;Paul T Spellman;Katrin Lorenz;Eva H Lee;Mary Helen Barcellos-Hoff;Ole W Petersen;Joe W Gray;Mina J Bissell - Molecular oncology (2007)
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Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells. - Nesrin Tüysüz;Louis van Bloois;Stieneke van den Brink;Harry Begthel;Monique M A Verstegen;Luis J Cruz;Lijian Hui;Luc J W van der Laan;Jeroen de Jonge;Robert Vries;Eric Braakman;Enrico Mastrobattista;Jan J Cornelissen;Hans Clevers;Derk Ten Berge - Nature communications (2017)
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Cadmium Exposure Inhibits Branching Morphogenesis and Causes Alterations Consistent With HIF-1α Inhibition in Human Primary Breast Organoids. - Sabrina A Rocco;Lada Koneva;Lauren Y M Middleton;Tasha Thong;Sumeet Solanki;Sarah Karram;Kowit Nambunmee;Craig Harris;Laura S Rozek;Maureen A Sartor;Yatrik M Shah;Justin A Colacino - Toxicological sciences : an official journal of the Society of Toxicology (2018)

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... (198 更多篇文献)

Next-generation cancer organoids. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​