ROS1-positive non-small cell lung cancer (NSCLC): biology, diagnostics, therapeutics and resistance

被引:26
作者
Yu, Zhi-Qiong [1 ]
Wang, Meng [1 ]
Zhou, Wen [1 ]
Mao, Meng-Xia [1 ]
Chen, Yuan-Yuan [1 ]
Li, Na [1 ]
Peng, Xiao-Chun [2 ,3 ]
Cai, Jun [1 ]
Cai, Zhi-Qiang [1 ]
机构
[1] Yangtze Univ, Dept Oncol, Affiliated Hosp 1, 1 Nanhuan Rd, Jingzhou 434023, Hubei, Peoples R China
[2] Ctr Mol Med, Lab Oncol, Jingzhou, Peoples R China
[3] Yangtze Univ, Hlth Sci Ctr, Sch Basic Med, Dept Pathophysiol, 1 Nanhuan Rd, Jingzhou 434023, Peoples R China
关键词
Non-small cell lung cancer; ROS1-positive; diagnostics; drug resistance; targeted therapies; 2ND-GENERATION ALK INHIBITORS; PEMETREXED-BASED CHEMOTHERAPY; TYROSINE KINASE INHIBITORS; ROS1; FUSION; OPEN-LABEL; INTEGRATED ANALYSIS; CRIZOTINIB RESISTANCE; ENDOPLASMIC-RETICULUM; ANTITUMOR-ACTIVITY; TARGETED THERAPY;
D O I
10.1080/1061186X.2022.2085730
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
ROS1 is a proto-oncogene encoding a receptor tyrosine protein kinase (RTK), homologous to the v - Ros sequence of University of Manchester tumours virus 2 (UR2) sarcoma virus, whose ligands are still being investigated. ROS1 fusion genes have been identified in various types of tumours. As an oncoprotein, it promotes cell proliferation, activation and cell cycle progression by activating downstream signalling pathways, accelerating the development and progression of non-small cell lung cancer (NSCLC). Studies have demonstrated that ROS1 inhibitors are effective in patients with ROS1-positive NSCLC and are used for first-line clinical treatment. These small molecule inhibitors provide a rational therapeutic option for the treatment of ROS1-positive patients. Inevitably, ROS1 inhibitor resistance mutations occur, leading to tumours recurrence or progression. Here, we comprehensively review the identified biological properties and Differential subcellular localisation of ROS1 fusion oncoprotein promotes tumours progression. We summarise recently completed and ongoing clinical trials of the classic and new ROS1 inhibitors. More importantly, we classify the complex evolving tumours cell resistance mechanisms. This review contributes to our understanding of the biological properties of ROS1 and current therapeutic advances and resistant tumours cells, and the future directions to develop ROS1 inhibitors with durable effects.
引用
收藏
页码:845 / 857
页数:13
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