Li Lin, Huang Weixue, Ren Xiaomei, Wang Zhen, Ding Ke, Zhao Linxiang, Zhang Jinwei
State Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
State Key Laboratory of Chemical Biology, Research Center of Chemical Kinomics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China.
Sci China Life Sci. 2024 Dec;67(12):2603-2616. doi: 10.1007/s11427-024-2685-9. Epub 2024 Aug 12.
While receptor tyrosine kinase-like orphan receptor 1 (ROR1) is typically expressed at low levels or absent in normal tissues, its expression is notably elevated in various malignant tumors and conditions, including chronic lymphocytic leukemia (CLL), breast cancer, ovarian cancer, melanoma, and lung adenocarcinoma. This distinctive feature positions ROR1 as an attractive target for tumor-specific treatments. Currently, several targeted drugs directed at ROR1 are undergoing clinical development, including monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor T-cell therapy (CAR-T). Additionally, there are four small molecule inhibitors designed to bind to ROR1, presenting promising avenues for the development of PROTAC degraders targeting ROR1. This review offers updated insights into ROR1's structural and functional characteristics, embryonic development implications, cell survival signaling pathways, and evolutionary targeting strategies, all of which have the potential to advance the treatment of malignant tumors.
受体酪氨酸激酶样孤儿受体1（ROR1）通常在正常组织中低水平表达或不表达，但其在各种恶性肿瘤和病症中表达显著升高，包括慢性淋巴细胞白血病（CLL）、乳腺癌、卵巢癌、黑色素瘤和肺腺癌。这一独特特征使ROR1成为肿瘤特异性治疗的一个有吸引力的靶点。目前，几种针对ROR1的靶向药物正在进行临床开发，包括单克隆抗体、抗体药物偶联物（ADC）和嵌合抗原受体T细胞疗法（CAR-T）。此外，有四种设计用于与ROR1结合的小分子抑制剂，为开发靶向ROR1的PROTAC降解剂提供了有前景的途径。本综述提供了关于ROR1的结构和功能特征、胚胎发育意义、细胞存活信号通路以及进化靶向策略的最新见解，所有这些都有可能推动恶性肿瘤的治疗。
