INSERM, IMRB (Clinical Epidemiology and Ageing Unit), University Paris Est Créteil, F-94010 Créteil, France.
Pneumology Department, Centre Hospitalier Intercommunal de Créteil, 40, Avenue de Verdun, F-94010 Créteil, France.
Curr Oncol. 2022 Jan 28;29(2):641-658. doi: 10.3390/curroncol29020057.
The gene plays a major role in the oncogenesis of numerous tumors. rearrangement is found in 0.9-2.6% of non-small-cell lung cancers (NSCLCs), mostly lung adenocarcinomas, with a significantly higher rate of women, non-smokers, and a tendency to a younger age. It has been demonstrated that is a true oncogenic driver, and tyrosine kinase inhibitors (TKIs) targeting ROS-1 can block tumor growth and provide clinical benefit for the patient. Since 2016, crizotinib has been the first-line reference therapy, with two-thirds of the patients' tumors responding and progression-free survival lasting ~20 months. More recently developed are ROS-1-targeting TKIs that are active against resistance mechanisms appearing under crizotinib and have better brain penetration. This review summarizes current knowledge on rearrangement in NSCLCs, including the mechanisms responsible for oncogenicity, epidemiology of -positive tumors, methods for detecting rearrangement, phenotypic, histological, and molecular characteristics, and their therapeutic management. Much of this work is devoted to resistance mechanisms and the development of promising new molecules.
该基因在许多肿瘤的癌发生中起主要作用。重排在非小细胞肺癌（NSCLC）中的发生率为 0.9-2.6%，主要为肺腺癌，女性、不吸烟者的发生率较高，且有年轻化趋势。已经证实 是一种真正的致癌驱动基因，针对 ROS-1 的酪氨酸激酶抑制剂（TKI）可以阻断肿瘤生长，并为患者提供临床获益。自 2016 年以来，克唑替尼已成为一线参考治疗药物，三分之二的患者肿瘤有反应，无进展生存期持续约 20 个月。最近开发的针对 ROS-1 的 TKI 对克唑替尼出现的耐药机制有效，且具有更好的脑穿透性。这篇综述总结了 NSCLC 中 重排的最新知识，包括导致致癌性的机制、阳性肿瘤的流行病学、重排检测方法、表型、组织学和分子特征，以及它们的治疗管理。其中很大一部分工作致力于耐药机制和有前途的新分子的开发。
