三阴性乳腺癌(TNBC)对大多数内分泌治疗及针对HER-2、ER、PR的靶向治疗药物不敏感，因此，寻找TNBC新的靶点和靶向治疗药物是乳腺癌研究亟待解决的问题。课题组前期研究发现新型小分子酪氨酸激酶抑制剂DCC-2036可抑制TNBC MDA-MB-231细胞的增殖和侵袭转移能力并诱导细胞凋亡，且其对细胞增殖的抑制作用优于5-FU和Gefitinib等临床治疗药物。同时，我们还初步证实受体酪氨酸激酶AXL可能是DCC-2036在TNBC细胞中发挥作用的关键靶点。基于此，我们推测DCC-2036可通过靶向AXL进而调控其下游信号通路在TNBC中发挥抗肿瘤作用。本课题拟证实DCC-2036对TNBC的抗肿瘤作用，并揭示其在抗TNBC中的作用靶点和相关机制，课题的完成可为DCC-2036用于临床治疗TNBC提供理论基础和实验依据，为临床药物耐受性TNBC提供潜在的治疗靶点。

Triple negative breast cancer (TNBC) is insensitive to endocrine therapy and targeted therapy on HER-2, ER, PR. Therefore, there is a desperate need to find new targets and new targeted therapeutic drugs for TNBC in breast cancer research. Our previous studies have confirmed that the novel small molecule tyrosine kinase inhibitor DCC-2036 could inhibit proliferation, invasion, migration and induce apoptosis in TNBC MDA-MB-231 cells. Moreover, its inhibitory effect on cell proliferation was better than some clinical treatments such as 5-FU and Gefitinib. We also confirmed the receptor tyrosine kinase AXL might be the key target of DCC-2036 in TNBC cells. Based on this, we speculate that DCC-2036 would target AXL and then regulate its downstream signaling pathways to exert its anti-tumor effect in TNBC. This project will focus on demonstrating the anti-tumor effect of DCC-2036 in TNBC, and revealing its critical targets and related molecular mechanisms. The completion of this project would provide a theoretical basis and experimental evidence for DCC-2036 used in the clinical treatment of TNBC, and provide potential therapeutic targets for TNBC with clinical drug resistance.