目前，除了EGFR和ALK之外大部分非小细胞肺癌（NSCLC）分子分型还未明确鉴定，临床上缺乏特异的治疗靶点。因此，寻找新的分子靶标，细化肿瘤分子分型，对NSCLC个体化治疗至关重要。研究表明，携带ROS1基因融合的NSCLC患者能从克唑替尼治疗中获益。我们前期研究发现，ROS1基因融合的患者癌组织中Cyclin D1和Ki67表达明显增加，过表达ROS1融合基因的NSCLC细胞增殖速度加快，体内成瘤能力增强。这些证据表明，ROS1融合基因可能成为新的NSCLC分子分型标志，系统研究其生物学功能，阐明其作用机制有重要的临床意义。本课题拟在上述工作基础上，全面评价ROS1基因融合对NSCLC细胞恶性生物学行为的影响，筛选验证ROS1下游的信号转导通路，建立针对ROS1基因融合的抗肿瘤药物反应谱。本课题的开展将为ROS1基因融合在NSCLC中所发挥的作用提供直接的证据和有益的理论依据。

Although EGFR mutation and ALK rearrangement are two well-known molecular subtypes in NSCLC, the clinical treatments of NSCLC patients are trapped owing to the shortage of definite therapeutic targets for the remaining patients. Therefore, it is essential for researchers to refine the molecular subtype and find new molecular targets in NSCLC individualized treatment. Several studies showed that NSCLC patients with ROS1 rearrangement could benefit from crizotinib. And our previous study also demonstrated that the expressions of Cyclin D1 and Ki67 were increased in the tumor issue of NSCLC patients with ROS1 rearrangement. In addition, the ability of proliferation and tumorigenicity is elevated in tumor cells with ROS1 rearrangement. All the previous evidences implied that ROS1 rearrangement probably stands for a new molecular subtype in NSCLC, and a clear understanding of its biological function and underlying molecular mechanism has great clinical significance which will broaden the treatments and offer new opportunities for patients. This study will comprehensively evaluate the the effect of ROS1 rearrangement on NSCLC maligant behavior, screen and verify ROS1 downstream signal transduction pathways, and establish the anticancer drugs spectrum. The successful implementation of this study will provide the direct evidence and useful theoretical basis for ROS1 gene rearrangement in NSCLC treatment.