尽管传统治疗乳腺癌的方法对癌症病人有一定的帮助，但是大多数已经发生转移的病人经传统方法治疗之后都会复发，这是由于传统治疗方法无法杀免肿瘤干细胞，肿瘤干细胞是肿瘤中存在的一个很小的细胞亚群，该亚群具有自我更新和分化的能力，从而能够致使肿瘤发生，发展和转移。ROR1是在胚胎期表达而在成人组织中不再表达的I型孤儿受体络氨酸激酶，最近研究表明其在许多癌症中包括乳腺癌中又重新表达，其表达和上皮间质转化(EMT)，乳腺癌的转移和复发密切相关，可是，ROR1是否在乳腺癌肿瘤干细胞中起作用及其作用机理并不清楚。本研究将采用 PDX小鼠模型，通过生物信息学和质谱分析确定与ROR1相互作用的蛋白及信号通路，进而确定ROR1及其互作蛋白和所激活的信号通路对肿瘤干细胞干性维持的作用。通过该研究，我们将会鉴定出乳腺癌肿瘤干细胞的新靶点及其该靶点的作用机理，从而有助于开发可以清除肿瘤干细胞的靶向药物。

Despite recent advances, many patients with breast cancer relapse after apparently responding well to chemotherapy, often developing metastatic disease. This is thought due to the post-treatment survival of a small number of breast cancer stem cells (CSC), which are relatively resistant to chemotherapy, have self-renewal capacity, can repopulate the tumor, and spread to distant sites. Therefore, identification of new surface protein specifically expressed on the breast cancer stem cell (CSC) will help develop novel approach to eradicate breast CSC to improve clinical outcome of treatment for patient with breast cancer. ROR1, a receptor tyrosine kinase (RTK)–like orphan receptor that ordinarily is expressed during embryogenesis, then is found on neoplastic cells of many different types of cancer, but not on normal adult tissues. Moreover, ROR1 is expressed on less well-differentiated tumors that have high potential for relapse and metastasis and that also express markers associated with the EMT. However, ROR1 function in breast CSC remains unknown. Therefore, we will use patient-derived xenograft (PDX) mice model to perform functional study to examine the role of ROR1 and/or its associated proteins in breast CSC. We will also explore mechanism underlying the function of ROR1 and its associated proteins in breast CSC. Through successfully completion of this project, we will identify new targets for breast CSC and also determine activated signaling pathway in CSCs.