Assessing therapy response in patient-derived xenografts
Assessing therapy response in patient-derived xenografts
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DOI：
10.1126/scitranslmed.abf4969
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发表时间：
2021-11-17
影响因子：
17.1
通讯作者：
Goldenberg，Anna
中科院分区：
文献类型：
--
作者：
Ortmann，Janosch;Rampasek，Ladislav;Goldenberg，Anna
在人类癌症小鼠模型中量化对药物治疗的反应对于治疗开发和分配很重要，但仍然是一项具有挑战性的任务。为了能够更容易地转化实验结果，量化该响应的优选测量应考虑更多可用的实验数据，包括随时间推移的肿瘤大小和重复之间的变化。我们提出了一个理论上接地的措施，KuLGaP，计算治疗和对照组之间的差异。我们使用329个患者来源的异种移植（PDX）模型测试和比较KuLGaP与四种广泛使用的反应措施。我们的研究结果表明，KuLGaP比目前现有的措施更具选择性，降低了假阳性呼叫的风险，并提高了实验室结果向临床实践的转化。我们还表明，与其他应对措施相比，人类治疗的结果与KuLGaP措施的结果更一致。KuLGaP有可能成为量化小鼠模型中药物治疗的首选指标，因为它可以通过www.example.com网站轻松使用。
Quantifying response to drug treatment in mouse models of human cancer is important for treatment development and assignment, yet remains a challenging task. To be able to translate the results of the experiments more readily, a preferred measure to quantify this response should take into account more of the available experimental data, including both tumor size over time and the variation among replicates. We propose a theoretically grounded measure, KuLGaP, to compute the difference between the treatment and control arms. We test and compare KuLGaP to four widely used response measures using 329 patient-derived xenograft (PDX) models. Our results show that KuLGaP is more selective than currently existing measures, reduces the risk of false-positive calls, and improves translation of the laboratory results to clinical practice. We also show that outcomes of human treatment better align with the results of the KuLGaP measure than other response measures. KuLGaP has the potential to become a measure of choice for quantifying drug treatment in mouse models as it can be easily used via the kulgap.ca website.