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Applications of patient-derived tumor xenograft models and tumor organoids.
Journal of Hematology & Oncology ( IF 28.5 ) Pub Date : 2020-01-07 , DOI: 10.1186/s13045-019-0829-z
Go J Yoshida 1, 2
Affiliation  

Patient-derived tumor xenografts (PDXs), in which tumor fragments surgically dissected from cancer patients are directly transplanted into immunodeficient mice, have emerged as a useful model for translational research aimed at facilitating precision medicine. PDX susceptibility to anti-cancer drugs is closely correlated with clinical data in patients, from whom PDX models have been derived. Accumulating evidence suggests that PDX models are highly effective in predicting the efficacy of both conventional and novel anti-cancer therapeutics. This also allows "co-clinical trials," in which pre-clinical investigations in vivo and clinical trials could be performed in parallel or sequentially to assess drug efficacy in patients and PDXs. However, tumor heterogeneity present in PDX models and in the original tumor samples constitutes an obstacle for application of PDX models. Moreover, human stromal cells originally present in tumors dissected from patients are gradually replaced by host stromal cells as the xenograft grows. This replacement by murine stroma could preclude analysis of human tumor-stroma interactions, as some mouse stromal cytokines might not affect human carcinoma cells in PDX models. The present review highlights the biological and clinical significance of PDX models and three-dimensional patient-derived tumor organoid cultures of several kinds of solid tumors, such as those of the colon, pancreas, brain, breast, lung, skin, and ovary.

中文翻译:

患者来源的肿瘤异种移植模型和肿瘤类器官的应用。

源自患者的肿瘤异种移植物(PDXs)已成为一种有用的模型,旨在促进精密医学的应用,在这种肿瘤异种移植物中,将从癌症患者手术切除的肿瘤片段直接移植到免疫缺陷小鼠中。PDX对抗癌药的敏感性与患者的临床数据密切相关,从中得出了PDX模型。越来越多的证据表明,PDX模型在预测常规和新型抗癌疗法的疗效方面非常有效。这也允许进行“临床前试验”,其中可以并行或先后进行体内临床前研究和临床试验,以评估患者和PDXs的药物疗效。然而,PDX模型和原始肿瘤样品中存在的肿瘤异质性构成了PDX模型应用的障碍。此外,随着异种移植物的生长,最初存在于从患者身上解剖的肿瘤中的人类基质细胞逐渐被宿主基质细胞替代。由于某些小鼠基质细胞因子可能不会影响PDX模型中的人类癌细胞,因此这种被鼠基质替代的方法可能无法分析人类肿瘤与基质的相互作用。本综述着重介绍了PDX模型和几种实体瘤(例如结肠,胰腺,脑,乳腺,肺,皮肤,卵巢等)的三维患者源性肿瘤类器官培养物的生物学和临床意义。随着异种移植物的生长,最初存在于从患者身上解剖出来的肿瘤中的人类基质细胞逐渐被宿主基质细胞所替代。由于某些小鼠基质细胞因子可能不会影响PDX模型中的人类癌细胞,因此这种被鼠基质替代的方法可能无法分析人类肿瘤与基质的相互作用。本综述着重介绍了PDX模型和几种实体瘤(例如结肠,胰腺,脑,乳腺,肺,皮肤,卵巢等)的三维患者源性肿瘤类器官培养物的生物学和临床意义。随着异种移植物的生长,最初存在于从患者身上解剖出来的肿瘤中的人类基质细胞逐渐被宿主基质细胞所替代。由于某些小鼠基质细胞因子可能不会影响PDX模型中的人类癌细胞,因此这种被鼠基质替代的方法可能无法分析人类肿瘤与基质的相互作用。本综述着重介绍了PDX模型和几种实体瘤(例如结肠,胰腺,脑,乳腺,肺,皮肤,卵巢等)的三维患者源性肿瘤类器官培养物的生物学和临床意义。
更新日期:2020-04-22
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