Tigu Adrian-Bogdan, Munteanu Raluca, Moldovan Cristian, Rares Drula, Kegyes David, Tomai Radu, Moisoiu Vlad, Ghiaur Gabriel, Tomuleasa Ciprian, Einsele Hermann, Gulei Diana, Croce Carlo M
Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca, Cluj Napoca, Romania.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cell Death Discov. 2024 Nov 17;10(1):471. doi: 10.1038/s41420-024-02239-1.
Receptor tyrosine kinases (RTKs) are key cell surface receptors involved in cell communication and signal transduction, with great importance in cell growth, differentiation, survival, and metabolism. Dysregulation of RTKs, such as EGFR, VEGFR, HER2 or ROR, could lead to various diseases, particularly cancers. ROR1 has emerged as a promising target in hematological malignancies. The development of ROR1 targeted therapies is continuously growing leading to remarkable novel therapeutical approaches using mAbs, antibody-drug conjugates, several small molecules or CAR T cells which have shown encouraging preclinical results. In the hematological field, mAbs, small molecules, BiTEs or CAR T cell therapies displayed promising outcomes with the clinical trials data encouraging the use of anti-ROR1 therapies. This paper aims to offer a comprehensive analysis of the current landscape of ROR1-targeted therapies in hematological malignancies marking the innovative approaches with promising preclinical and clinical. Offering a better understanding of structural and functional aspects of ROR1 could lead to new perspectives in targeting a wide spectrum of malignancies.
受体酪氨酸激酶（RTKs）是参与细胞通讯和信号转导的关键细胞表面受体，在细胞生长、分化、存活和代谢中具有重要意义。RTKs的失调，如表皮生长因子受体（EGFR）、血管内皮生长因子受体（VEGFR）、人表皮生长因子受体2（HER2）或受体酪氨酸激酶样孤儿受体1（ROR1），可能导致各种疾病，尤其是癌症。ROR1已成为血液系统恶性肿瘤中一个有前景的靶点。针对ROR1的治疗方法不断发展，催生出了使用单克隆抗体（mAbs）、抗体药物偶联物、多种小分子或嵌合抗原受体T细胞（CAR T细胞）的显著新颖治疗方法，这些方法在临床前研究中显示出令人鼓舞的结果。在血液学领域，单克隆抗体、小分子、双特异性T细胞衔接器（BiTEs）或CAR T细胞疗法取得了有前景的成果，临床试验数据也鼓励使用抗ROR1疗法。本文旨在全面分析血液系统恶性肿瘤中针对ROR1治疗方法的当前形势，突出具有前景的临床前和临床创新方法。更好地理解ROR1的结构和功能方面可能会为靶向多种恶性肿瘤带来新的视角。
