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Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week
Nature Communications ( IF 14.7 ) Pub Date : 2021-05-10 , DOI: 10.1038/s41467-021-22676-1
Yawei Hu 1 , Xizhao Sui 2 , Fan Song 3 , Yaqian Li 3 , Kaiyi Li 1 , Zhongyao Chen 1 , Fan Yang 2 , Xiuyuan Chen 2 , Yaohua Zhang 3 , Xianning Wang 4 , Qiang Liu 5 , Cong Li 6 , Binbin Zou 6 , Xiaofang Chen 3, 7 , Jun Wang 2 , Peng Liu 1
Affiliation  

While the potential of patient-derived organoids (PDOs) to predict patients’ responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.



中文翻译:


通过微孔阵列分析肺癌类器官可预测患者一周内的药物反应



虽然患者源性类器官(PDO)预测患者抗癌治疗反应的潜力已得到广泛认可,但建立 PDO 的时间长且效率低,阻碍了基于 PDO 的药物敏感性测试在临床中的实施。我们首先采用机械样品处理方法,从手术切除和活检的肿瘤组织中生成肺癌类器官(LCO)。 LCO 概括了亲代肿瘤的组织学和遗传特征,并且具有无限扩展的潜力。通过采用集成的超疏水微孔阵列芯片(InSMAR-chip),我们证明了数百个 LCO(可以从第 0 代的大多数样品中生成的数量)足以在一周内产生有临床意义的药物反应。结果证明,我们为期一周的药物测试与患者来源的异种移植、肿瘤基因突变和临床结果非常一致。 LCO 模型与微孔装置相结合,为预测临床环境中患者特异性药物反应提供了技术上可行的方法。

更新日期:2021-05-10
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