常规放化疗之后许多肿瘤病人再次复发，并常伴随着肿瘤转移，主要原因是，放化疗之后残存的肿瘤中富集了一群具有干性特征和间质特征的细胞。这些细胞对放化疗有拮抗作用，具有自我更新和分化的能力，是肿瘤发生，发展，转移和复发的根源。ROR2是在胚胎期表达，在成人组织中很少表达，在乳腺癌中又重新表达的络氨酸激酶孤儿受体，其表达和上皮间质转化(EMT)密切相关。尽管诱导EMT可以诱导非肿瘤干细胞转化为肿瘤干细胞，但ROR2是否在肿瘤干细胞中起作用，是否靶向攻击ROR2可以抑制肿瘤的转移和复发并不清楚。本研究采用 PDX小鼠模型及organoid类器官模型，分析并确定ROR2在肿瘤干细胞及EMT中的作用及作用机理，并测试我们新开发的抗ROR2的单克隆抗体是否可以抑制乳腺癌的疾病进展。通过该研究，我们将鉴定出致使肿瘤转移及复发的新靶点，并开发出可以抑制乳腺癌转移及复发的一类靶向新药。

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 cells with mesenchymal or stemness feature. These cells called cancer stem cells (CSCs) or tumor initiation cells (TIC) have self-renewal capacity, can repopulate the tumor, and spread to distant sites. ROR2, 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, expression of ROR2 in breast cancer is associated with epithelial-mesenchymal transition (EMT) and tumor metastasis. However, lacking is evidence that ROR2 is associated with breast cancer stemness or targeting ROR2 can repress breast cancer metastasis and relapse. Therefore, we will use patient-derived xenograft (PDX) mice model and/or organoid to perform functional study to examine the role of ROR2 and explore mechanism underlying the function of ROR2 in breast cancer. Finally, we examine if targeting ROR2 using our newly developed anti-ROR2 monoclonal antibody can successfully repress tumor metastasis and relapse. Through successfully completion of this project, we will identify new targets for breast cancer metastasis and relapse, and also develop novel therapeutics for targeting breast cancer to prevent tumor metastasis and/or relapse.