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Patient-derived xenografts as preclinical neuroblastoma models

机译：患者衍生的异种移植物作为临床前神经母细胞瘤模型

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The prognosis for children with high-risk neuroblastoma is often poor and survivors can suffer from severe side effects. Predictive preclinical models and novel therapeutic strategies for high-risk disease are therefore a clinical imperative. However, conventional cancer cell line-derived xenografts can deviate substantially from patient tumors in terms of their molecular and phenotypic features. Patient-derived xenografts (PDXs) recapitulate many biologically and clinically relevant features of human cancers. Importantly, PDXs can closely parallel clinical features and outcome and serve as excellent models for biomarker and preclinical drug development. Here, we review progress in and applications of neuroblastoma PDX models. Neuroblastoma orthotopic PDXs share the molecular characteristics, neuroblastoma markers, invasive properties and tumor stroma of aggressive patient tumors and retain spontaneous metastatic capacity to distant organs including bone marrow. The recent identification of genomic changes in relapsed neuroblastomas opens up opportunities to target treatment-resistant tumors in well-characterized neuroblastoma PDXs. We highlight and discuss the features and various sources of neuroblastoma PDXs, methodological considerations when establishing neuroblastoma PDXs, in vitro 3D models, current limitations of PDX models and their application to preclinical drug testing.
机译：高风险神经母细胞瘤的儿童预后通常贫瘠，幸存者可以患有严重的副作用。因此，高危疾病的预测临床前模型和新的治疗策略是一种临床迫切。然而，在其分子和表型特征方面，常规的癌细胞系衍生的异种移植物可以基本上从患者肿瘤偏离。患者衍生的异种移植物（PDXS）概括了人类癌症的许多生物学和临床相关特征。重要的是，PDXS可以密切平行临床特征和结果，并作为生物标志物和临床前药物发育的优秀模型。在这里，我们审查了神经母细胞瘤PDX模型的进展和应用。神经母细胞瘤原位PDXs分子特征，神经母细胞瘤标志物，侵袭性患者肿瘤的侵袭性和肿瘤基质，并保持自发转移能力，包括骨髓，包括骨髓。最近识别复发神经细胞组织的基因组变化使机会靶向靶向抗性的神经母细胞瘤PDX。我们突出显示并讨论了神经母细胞瘤PDX的特征和各种来源，在建立神经母细胞瘤PDX时，体外3D模型，PDX模型的电流限制及其在临床前药物检测中的应用。

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