Qin Xinchen, Zhang Yao, Yu Haijie, Ma Lijuan
Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China.
Zhongguo Fei Ai Za Zhi. 2023 Apr 20;26(4):310-318. doi: 10.3779/j.issn.1009-3419.2023.101.13.
Spindle assembly checkpoint (SAC) is a protective mechanism for cells to undergo accurate mitosis. SAC prevented chromosome segregation when kinetochores were not, or incorrectly attached to microtubules in the anaphase of mitosis, thus avoiding aneuploid chromosomes in daughter cells. Aneuploidy and altered expression of SAC component proteins are common in different cancers, including lung cancer. Therefore, SAC is a potential new target for lung cancer therapy. Five small molecule inhibitors of monopolar spindle 1 (MPS1), an upstream component protein of SAC, have entered clinical trials. This article introduces the biological functions of SAC, summarizes the abnormal expression of SAC component proteins in various cancers and the research progress of MPS1 inhibitors, and expects to provide a reference for the future development of lung cancer therapeutic strategies targeting SAC components. .
纺锤体组装检查点(SAC)是细胞进行精确有丝分裂的一种保护机制。当动粒在有丝分裂后期未附着或错误地附着于微管时,SAC可阻止染色体分离,从而避免子细胞中出现非整倍体染色体。非整倍体以及SAC组成蛋白的表达改变在包括肺癌在内的不同癌症中很常见。因此,SAC是肺癌治疗的一个潜在新靶点。SAC的上游组成蛋白单极纺锤体1(MPS1)的5种小分子抑制剂已进入临床试验。本文介绍了SAC的生物学功能,总结了SAC组成蛋白在各种癌症中的异常表达以及MPS1抑制剂的研究进展,期望为未来针对SAC组分的肺癌治疗策略的发展提供参考。