近年来，口服多靶点药物Dasatinib在实体瘤中的应用受到广泛关注，但不合适的病人选择严重制约了其临床疗效，因此开发Dasatinib敏感预测标志物是目前亟需解决的关键问题。本课题以前期所获得的对Dasatinib敏感的PDX动物模型为研究对象，拟通过外显子组测序或芯片杂交技术检测敏感模型组织基因组遗传背景特征筛选潜在敏感标志物，进一步通过系统的体内外实验进行相关性验证和获得敏感性的机制探讨，在此基础上，通过另一组PDX模型筛选出标志物阳性群体进行贴近临床式的标志物阳性选择性试验(one-arm adaptive trial)，以考察标志物是否具有独立的预测能力。通过本研究旨在获得数个具有临床潜在应用价值的敏感标志物，为Dasatinib在实体瘤病人中选择合适的敏感人群进行个体化治疗提供理论依据和相关的检测指标。

In recent years, dasatinib, an oral available multi-target tyrosine kinase inhibitor, has been tested for its efficacy in several types of solid tumors beyond its original application in CML. However, the response ratio of dasatinib in clinical patients was limited in unselected populations, so it's of urgent need to identify the appropriate predictive bimarkers for dasatinib. In this study, we designed to take advantage of the next-generation sequence technology and SNP array to analyze the genomic background and explore the potential predictive biomarkers for dasatinib in patient derived xenograft models which obtained sensitivity to dasatinib. Then, the correlation and underlied molecular mecanisms of drug sensitivity and biomarkers will be tested in vitro and in vivo. Finally, the predict power of these potential biomarkers will be examined in a seprate and independent group of patient derived xenograft models whose expression of these biomarkers are positive, which mimic the clinical one-arm adaptive trials. The aim of this study is to find out several clinical applicable predictive biomkers to select the most responsive subpopulations for more successful personalized medicine of dasatinib in clinic.