PDX和PDO我知道了，什么是PDXO？

PDO项目启动后的第1篇科普短文

are 3D in vitro models generated from patient tumor tissue that’s been previously passaged into murine models for expansion. More simply, PDXO are in vitro models derived from in vivo .

是用前期已经传代到小鼠模型用于扩增的患者肿瘤组织制作的三维体外模型，更简单地说，PDXO是来自于体内PDX的体外模型。

PDXOs are generated using the same protocols as patient-derived organoids (PDO, developed directly from patient tumor tissue). For both models, cancer stem cells (CSCs) are preserved and give rise to cancers found in human patients. PDXO derivation methods include protocols which are optimized and adapted for the growth of tumor organoids.

PDXOs是用与PDO（患者来源的类器官，直接从患者肿瘤组织开发来的）相同的操作方法制作出来的。对于两种模型，肿瘤干细胞都被保存下来并产生癌症（与患者中的是一样的）。PDXO的制备方法包括来源于已优化的并适用于肿瘤类器官生长的的protocols。

Briefly, PDX tumor cells are cultured in a highly enriched growth medium containing a tailored cocktail of growth factors. This allows the long-term expansion of CSCs and their progeny, with high stability and genomic integrity. This leads to multicellular 3D PDX-derived organoids composed of different cell types reflecting those in the original patient tumor.

简单来讲，PDX肿瘤细胞培养在一个富含定制生长因子的培养基中。这为肿瘤干细胞（CSCs）及其后代提供了长期扩增的条件，使得多细胞的三维PDX来源的类器官反映了原始患者肿瘤中的不同细胞类型。

Since PDXOs derive from cancer stem cells, they faithfully recapitulate the histopathological properties of the corresponding in vivo PDX tumor (features which are lost in conventional in vitro models). PDXO models also retain key genomic and phenotypic features from the patient’s primary tumor. This results in a robust in vitro 3D model for cancer research and drug discovery.

自从肿瘤干细胞衍生出PDXOs，它们能如实概括出体内PDX肿瘤相应的组织病理特征，而在传统体外模型中这些特征是会丢失的。PDXO也可以保持患者原发性肿瘤关键的基因组和表观特征。这将促进这个强大的体外3D模型在癌症研究和药物研发中的应用。

Traditional oncology drug development strategies are failing. Oncology agents have a higher attrition rate than other therapeutic areas, with drug efficacy rather than safety being the clinical stumbling block.

传统的肿瘤药物开发策略一直在挫败。肿瘤药物比其他治疗领域的药物损耗率更高，同时，药物的疗效，而不是安全性，是临床治疗的一个绊脚石。

There’s a clear need for advanced in vitro models with improved predictive power, and to guide more relevant in vivo model selection. Choosing more clinically relevant in vitro and in vivo models as early as possible will accelerate drug development, and make preclinical programs more cost-effective.

对体外模型升级，使其具有更好的预测作用，并指导相关性更好的体内模型的选择，是非常有必要的。尽早地选择临床相关性更强的体外和体内模型将会加速药物开发，让临床前项目更合算。

Importantly, improved models such as PDX-derived organoids can also help researchers develop a more complete understanding of which patient subgroups will respond to a therapy, and the underlying reasons why.

重要的是，改进的模型（例如PDX来源的类器官）同样可以帮助研究人员更完整地理解药物治疗哪一亚类患者会有效及其原因。

Developing a platform combining robust in vitro PDXO assays with matched in vivo PDX model response offers a unique preclinical workflow to translate preclinical efficacy findings into clinical success.

开发一个整合了强大体外PDXO试验与其对应的体内PDX模型响应的平台可提供独特的临床前流程将临床前疗效结果转化为临床上的成功。

To fully understand the value of PDX-derived organoids in vitro, it’s important to first understand the value of PDX models in vivo.

为了更好地理解体外PDX来源类器官的价值，首先要对PDX体内模型的价值有个理解是很重要的。

PDX are the best preclinical in vivo model for predicting clinical outcomes. This is because PDX faithfully recapitulate the genomic and phenotypic complexities observed in cancer tissue. As PDX are derived directly from patient tumor tissue (and never propagated in vitro on plastic), they show high genetic integrity relative to the original patient tumor. Panels of PDX models from a patient population also represent that populations’ tumor heterogeneity.

PDX是预测临床结果的最佳临床前体内模型。这是因为PDX如实地概括了在癌组织中观察到的基因组和表型复杂性。由于PDX直接源自患者肿瘤组织（并且从未在塑料介质上体外繁殖），因此，相对于原始患者肿瘤，它们显示出高度的遗传完整性。来自患者群体的PDX模型面板也代表了该群体的肿瘤异质性。

already exist for many different tumor types, including breast, colorectal, and lung cancer. These models are very well-characterized, with gene expression profiles, in vivo pharmacology, and protein biomarker detection data available. This means that large libraries of PDXOs can be established from available PDXs with relative ease and speed providing the only available in vitro system to display patient relevance.

已为许多不同肿瘤类型（包括乳腺癌，结直肠癌和肺癌）提供了大量的PDX模型。这些模型在基因表达谱，体内药理学和蛋白质生物标志物检测数据方面已获得很好的表征。这意味着可以以相对容易和快捷的方式从可用的PDX建立大型的PDXO库，从而提供唯一可用于显示患者相关性的体外系统。

Developing a large library of annotated and extensively characterized PDXO (similarly to their matched PDX), allows us to take full advantage of the panel as a surrogate for the cancer patient population in high throughput drug screens.

开发一个带有注释且全面表征的PDXO的大型库（类似于其对应的PDX），使我们能够充分利用该面板作为高通量药物筛选中大量癌症患者样本的替代品。

Therefore, in developing in vitro PDXOs with matched in vivo PDX counterparts a pioneering drug discovery platform is created, with the potential to dramatically improve preclinical predictivity.

因此，在开发具有匹配的体内PDX对应物的体外PDXO时，创建了一个开拓性的药物发现平台，该平台具有显著提高临床前预测性的潜力。

PDX-derived organoids offer significant advantages over standard 3D models such as spheroids. PDXO:

• Better recapitulate the original disease (histopathology and molecular pathology).
• Better mimic the original tumor architecture, which is known to influence drug response.
• Provide higher quality read-outs with lower batch to batch variation and high signal:noise ratio.
• Provide improved predictivity of tumor response in vivo.

与标准3D模型（例如球体）相比，PDX派生的类动物动物具有明显的优势。PDXO：

• 更好地概括原始疾病（组织病理学和分子病理学）特征。
• 更好地模拟原始的肿瘤结构，已知该结构会影响药物反应。
• 提供高质量的读数，批次间差异较小，信噪比高。
• 提供体内肿瘤反应的改善的预测能力。
  

Compared with in vivo models, PDXO are relatively easier and faster to establish. This means that PDXO are better suited to large scale studies (testing multiple agents and combinations) than PDX. This allows in vivo platforms to instead be used for more focused studies, and results in a cost reduction in preclinical screening.

与体内模型相比，PDXO相对更容易建立。这意味着与PDX相比，PDXO更适合大规模研究（测试多种试剂和组合）。这就允许将体内平台用于更集中的研究，并降低临床前筛查的成本。

As discussed above, PDX-derived organoids provide an easily scalable in vitro system for large scale screens to obtain initial drug sensitivity data. Agents can then be moved to a more complex in vivo system, using matched PDX derived from the same tumor tissue and cells as the PDXO. This allows the refinement and validation of your therapeutic strategy, in the first paired and most predictive platform of its kind.

如上所述，PDX来源的类器官为大规模筛选获得初始药物敏感性数据提供了易于扩展的体外系统。然后可以使用与PDXO来自相同肿瘤组织和细胞的匹配PDX，将药剂移至更复杂的体内系统。这可以在同类的第一个对应的且最具预测性的平台上完善和验证你的治疗策略。

Additionally, all the standard assays and techniques performed on cancer cell lines can also be performed on PDX-derived organoids, providing a versatile in vitro model. With the high level of genomic characterization data available, PDXO also provide a tool for in silico drug discovery.

另外，在癌细胞系上进行的所有标准测定和技术也可以在PDX来源的类器官上进行，从而提供了通用的体外模型。有了可用的高水平基因组表征数据，PDXO还可提供用于计算机药物发现的工具。

英文原文转自中美冠科生物官网，原创翻译，主要目的为传播学术。若认为侵权，请联系微信dswjhs删除。