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儿科固体瘤的患者衍生异种移植

Elizabeth Stewart^1,2, Sara M Federico¹, Xiang Chen³

¹Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

|August 31, 2017

概括

研究人员开发了来自患者的正位异位移植 (PDX) 来模拟儿科固体瘤,包括复发性疾病. 这种方法确定了药物脆弱性,显示了结合疗法在狂宫肌肉瘤PDX中实现了完整的反应.

科学领域:

癌症学
基因组学
翻译医学

背景情况:

儿童固体瘤的总生存率很高,但复发性疾病的生存率很低 (< 30%).
现有的模型难以捕捉儿童固体瘤的复杂性和多样性,尤其是复发性瘤.

研究的目的:

在诊断,复发和尸检时从儿科固体瘤中制造患者衍生异种移植 (PDX) 的方案.
建立可靠的PDX模型来研究儿科固体瘤异质性并确定治疗点.

主要方法:

收集了来自12种癌症的168名儿童的瘤样本.
通过基因表达特征分析,表观基因组学和基因组特征分析,确定了67个正位基因组XD.
在已建立的PDX模型中评估药物脆弱性.

主要成果:

确定的PDX准确地反映了患者瘤的分子形状.
基因组分析证实PDX复制了原始患者瘤的克隆群体.
鉴定了药物脆弱性,并证明WEE1抑制剂 (AZD1775),伊利诺特干和温克里斯的组合在体内得到了完全的响应.

结论:

整形PDX是捕捉儿科固体瘤复杂性的有价值模型,包括复发性疾病.
这些PDX模型有助于识别新的治疗策略和药物脆弱性.
结合使用AZD1775, irinotekan和vincristine的疗法在治疗狂宫肌肉瘤方面具有前景.

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