LeSavage Bauer L, Suhar Riley A, Broguiere Nicolas, Lutolf Matthias P, Heilshorn Sarah C
Department of Bioengineering, Stanford University, Stanford, CA, USA.
Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
Nat Mater. 2022 Feb;21(2):143-159. doi: 10.1038/s41563-021-01057-5. Epub 2021 Aug 12.
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.
患者特异性肿瘤的器官型模型正在彻底改变我们对癌症异质性及其对个性化医疗影响的理解。这些进展部分归因于类器官模型在体外稳定保留亲本肿瘤的遗传、蛋白质组学、形态学和药物表型特征的能力，同时还提供了前所未有的基因组和环境操纵。尽管最近类器官方案有创新，但由于包括癌症组织来源及后续处理、培养基配方和动物来源的三维基质等几个未标准化的方面，当前癌症类器官培养技术本质上是不受控制且不可重复的。鉴于癌症类器官有潜力准确概括与患者特异性癌症相关的肿瘤内和肿瘤间生物异质性，消除伴随癌症类器官培养的不良技术变异性对于建立可加速转化为患者护理见解的可重复平台是必要的。在此，我们描述了当前的挑战以及最近在标准化下一代癌症类器官系统方面的多学科进展和机遇。
