Therapeutic advances in the targeting of ROR1 in hematological cancers.

IF 6.1 2区生物学 Q1 CELL BIOLOGY Cell Death Discovery Pub Date : 2024-11-17 DOI:10.1038/s41420-024-02239-1

Adrian-Bogdan Tigu, Raluca Munteanu, Cristian Moldovan, Drula Rares, David Kegyes, Radu Tomai, Vlad Moisoiu, Gabriel Ghiaur, Ciprian Tomuleasa, Hermann Einsele, Diana Gulei, Carlo M Croce

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Abstract

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.

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针对血液肿瘤中 ROR1 的治疗进展。

受体酪氨酸激酶（RTK）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、存活和新陈代谢中具有重要作用。表皮生长因子受体（EGFR）、血管内皮生长因子受体（VEGFR）、HER2 或 ROR 等 RTK 的失调可导致各种疾病，尤其是癌症。ROR1 已成为血液恶性肿瘤中一个很有前景的靶点。ROR1 靶向疗法的开发正在不断发展，利用 mAbs、抗体药物共轭物、多种小分子或 CAR T 细胞的新型治疗方法令人瞩目，临床前研究结果令人鼓舞。在血液学领域，mAbs、小分子、BiTEs 或 CAR T 细胞疗法显示出了令人鼓舞的成果，临床试验数据鼓励使用抗 ROR1 疗法。本文旨在全面分析目前血液恶性肿瘤中 ROR1 靶向疗法的现状，指出临床前和临床中前景看好的创新方法。更好地了解 ROR1 的结构和功能可为靶向治疗各种恶性肿瘤提供新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.