本课题紧紧围绕肿瘤精准治疗的国际前沿，选择肿瘤研究领域重要的前沿靶点，聚焦个性化药物研发的核心瓶颈——耐药问题为突破口，同步关注肿瘤耐药的内外因—— “肿瘤”与“肿瘤微环境”，采用FGFR依赖的肿瘤细胞、多种基质细胞、获得性耐药细胞以及动物体内模型，首次探讨具有自主知识产权的新型FGFR抑制剂GF008获得性耐药的机制，探寻新的能够预测肿瘤患者对GF008耐药的生物标志物，并关注克服耐药的联合用药方案；预期研究成果将为推动GF008研发进程、指导GF008临床科学合理用药、实现个体化精准治疗提供重要的理论基础，为个性化创新药物研发提供范例。

With the increasing recognition of the importance of precision medicine in cancertherapy, the emergence of drug resistance has ultimately limited the benefit of targeted therapy, and presents a challenge to the treatment of cancer patients. In our laboratory, we have identified a novel, selective FGFR inhibitor candidate, designated as GF008. With the application of FGFR-addicted cancer cells, acquired-resistant cells, tumor stromal cells and xenografts, we will go insight into the mechanisms of action underlying the acquired resistance, especially the.potential role of tumor microenvironment in conferring GF008 resistance, which hopefully give rise to a rationale of drug combo-therapy for resistance. This study will provide further indication that the systematic dissection of interactions between tumor and their microenvironment can uncover important mechanisms underlying drug resistance. Expected esults will promote the drug development process of GF008 and provide preclinical evidence for GF008 clinical rational drug use to achieve precise individualized treatment. Further, this study provides example of personalized innovative drug research and development.