作者
Hui Gao, Joshua M Korn, Stéphane Ferretti, John E Monahan, Youzhen Wang, Mallika Singh, Chao Zhang, Christian Schnell, Guizhi Yang, Yun Zhang, O Alejandro Balbin, Stéphanie Barbe, Hongbo Cai, Fergal Casey, Susmita Chatterjee, Derek Y Chiang, Shannon Chuai, Shawn M Cogan, Scott D Collins, Ernesta Dammassa, Nicolas Ebel, Millicent Embry, John Green, Audrey Kauffmann, Colleen Kowal, Rebecca J Leary, Joseph Lehar, Ying Liang, Alice Loo, Edward Lorenzana, E Robert McDonald III, Margaret E McLaughlin, Jason Merkin, Ronald Meyer, Tara L Naylor, Montesa Patawaran, Anupama Reddy, Claudia Röelli, David A Ruddy, Fernando Salangsang, Francesca Santacroce, Angad P Singh, Yan Tang, Walter Tinetto, Sonja Tobler, Roberto Velazquez, Kavitha Venkatesan, Fabian Von Arx, Hui Qin Wang, Zongyao Wang, Marion Wiesmann, Daniel Wyss, Fiona Xu, Hans Bitter, Peter Atadja, Emma Lees, Francesco Hofmann, En Li, Nicholas Keen, Robert Cozens, Michael Rugaard Jensen, Nancy K Pryer, Juliet A Williams, William R Sellers
发表日期
2015/11/1
期刊
Nature medicine
卷号
21
期号
11
页码范围
1318-1325
出版商
Nature Publishing Group
简介
Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient responses for patient-selection strategies. We established ∼1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 × 1 × 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore …
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H Gao, JM Korn, S Ferretti, JE Monahan, Y Wang… - Nature medicine, 2015