| Autor: |
Fabian Von Arx, Fergal Casey, Sonja Tobler, Robert Cozens, Ying Liang, En Li, E. Robert McDonald, John Monahan, Audrey Kauffmann, Chao Zhang, Hans Bitter, Daniel Wyss, Mallika Singh, Edward Lorenzana, Tara L. Naylor, Francesco Hofmann, Rebecca Leary, Peter Atadja, Alice Loo, Fiona Xu, Anupama Reddy, Hongbo Cai, Ernesta Dammassa, Margaret E. McLaughlin, Shannon Chuai, Yun Zhang, Fernando Salangsang, Susmita Chatterjee, Christian Schnell, Stephanie Barbe, Hui Gao, Michael Rugaard Jensen, Youzhen Wang, Nicholas Keen, William R. Sellers, Millicent Embry, O. Alejandro Balbin, John Green, Marion Wiesmann, Joseph Lehar, Francesca Santacroce, Guizhi Yang, Claudia Roelli, Scott D. Collins, Kavitha Venkatesan, Colleen Kowal, Hui Qin Wang, Montesa Patawaran, Angad P Singh, Jason Merkin, Juliet Williams, Walter Tinetto, Roberto Velazquez, Emma Lees, Stephane Ferretti, Ronald Meyer, Nicolas Ebel, Shawn Cogan, Joshua M. Korn, David A. Ruddy, Zongyao Wang, Yan Tang, Derek Y. Chiang, Nancy Pryer |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Nature Medicine. 21:1318-1325 |
| ISSN: |
1546-170X
1078-8956 |
| Popis: |
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 propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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