Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR , Tehran , Iran +98 2122432020 ; +98 2122432021 ;
Expert Opin Ther Targets. 2015 Jul;19(7):941-55. doi: 10.1517/14728222.2015.1025753. Epub 2015 Apr 2.
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the receptor tyrosine kinase family. ROR1 is selectively overexpressed in a number of solid and hematological malignancies without significant expression in normal adult tissues. There are also some lines of evidence, which support the critical role of ROR1 in tumorigenesis. These characteristics introduce ROR1 as a suitable target for selective cancer immunotherapy. ROR1 targeting using different approaches such as siRNA, tyrosine kinase inhibitors and antibody induces tumor growth suppression in cancer cells.
The current review focuses on ROR1 structure and biological functions, expression profiles in normal and malignant tissues and its potential therapeutic applications in different malignancies. We aimed to encompass almost all important aspects of ROR1 biology and its importance in tumor targeted therapy approaches based on published papers in this field.
Considering ROR1 unique characters, it seems that it can pass most of the criteria for being an ideal target for cancer immunotherapy. ROR1 unique expression on cancer cells with subtle expression on normal tissues make it a suitable target with minimum potential side effects using different cancer therapy approaches such as mAb therapy, peptide and protein vaccination, cell therapy and small molecules.
受体酪氨酸激酶样孤儿受体 1(ROR1)是受体酪氨酸激酶家族的成员。ROR1 在许多实体瘤和血液恶性肿瘤中选择性过表达,而在正常成人组织中无明显表达。还有一些证据表明,ROR1 在肿瘤发生中起关键作用。这些特征使 ROR1 成为选择性癌症免疫治疗的合适靶点。使用不同方法(如 siRNA、酪氨酸激酶抑制剂和抗体)靶向 ROR1 可诱导癌细胞肿瘤生长抑制。
本综述重点介绍 ROR1 的结构和生物学功能、在正常和恶性组织中的表达谱及其在不同恶性肿瘤中的潜在治疗应用。我们旨在根据该领域已发表的论文,涵盖 ROR1 生物学及其在肿瘤靶向治疗方法中的重要性的几乎所有重要方面。
鉴于 ROR1 的独特特征,它似乎符合癌症免疫治疗的理想靶点的大多数标准。ROR1 在癌细胞上的独特表达,在正常组织上的轻微表达,使其成为使用 mAb 治疗、肽和蛋白疫苗接种、细胞治疗和小分子等不同癌症治疗方法的合适靶点,潜在副作用最小。