ALK二代抑制剂ZG006抗肿瘤药效学评价及克服Crizotinib耐药研究

本课题从"衡量靶向ALK药效活性"与"克服Crizotinib耐药特性"两个功能视角同步出发，一方面，采用ALK依赖的肿瘤细胞和裸鼠移植瘤模型，进行ZG006靶向ALK系统药效特性和作用机制研究；另一方面，采用ALK各耐药突变的工具体系、探讨ZG006克服突变耐药的潜力，构建Crizotinib获得性耐药体系，探寻潜在的代偿通路，并在此基础上探讨ZG006克服耐药的联合用药方案，从而全面评价ZG006克服Crizotinib耐药的潜力。本课题紧紧围绕抗肿瘤药物治疗的国际前沿，选择肿瘤研究领域重要的靶点为突破口，具有明显的针对性与目标性，积极研制具有我国自主知识产权的能够克服Crizotinib耐药的二代靶向ALK的抗肿瘤药物意义重大。

This project synchronization from the perspective of "measuring ALK targeting pharmacodynamic properties" and "overcoming Crizotinib resistance". On the one hand, with the applicaiton of ALK- tumor cells and xenografts, we evaluated ZG006 anti-tumor effcacy targeting ALK in vitro and in vivo. On the other hand, the use of ALK resistance mutant mode cell lines, to explore the potential of ZG006 overcome mutation mediated Crizotinib resistance, further constructing Crizotinib acquired resistance system, to explore the potential compensatory pathways, and then find out the right drug combination to overcome resisitance. This study focuses on the international front anticancer therapy and choosing the important target as a breakthrough. It's very important to develop second-generation ALK inhibitor with property to overcome Crizotininb resistance with our own intellectual property.