Zhao Kai, Li Xiangyu, Feng Yunxiang, Wang Jianming, Yao Wei
Department of Biliary and Pancreatic Surgery, Cancer Research Center Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Department of Thoracic Surgery Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Biomark Res. 2024 Mar 3;12(1):30. doi: 10.1186/s40364-024-00559-z.
As a major component of the digestive system malignancies, tumors originating from the hepatic and biliary ducts seriously endanger public health. The kinesins (KIFs) are molecular motors that enable the microtubule-dependent intracellular trafficking necessary for mitosis and meiosis. Normally, the stability of KIFs is essential to maintain cell proliferation and genetic homeostasis. However, aberrant KIFs activity may destroy this dynamic stability, leading to uncontrolled cell division and tumor initiation. In this work, we have made an integral summarization of the specific roles of KIFs in hepatocellular and biliary duct carcinogenesis, referring to aberrant signal transduction and the potential for prognostic evaluation. Additionally, current clinical applications of KIFs-targeted inhibitors have also been discussed, including their efficacy advantages, relationship with drug sensitivity or resistance, the feasibility of combination chemotherapy or other targeted agents, as well as the corresponding clinical trials. In conclusion, the abnormally activated KIFs participate in the regulation of tumor progression via a diverse range of mechanisms and are closely associated with tumor prognosis. Meanwhile, KIFs-aimed inhibitors also carry out a promising tumor-targeted therapeutic strategy that deserves to be further investigated in hepatobiliary carcinoma (HBC).
作为消化系统恶性肿瘤的主要组成部分，起源于肝内外胆管的肿瘤严重危害公众健康。驱动蛋白（KIFs）是分子马达，可实现有丝分裂和减数分裂所需的依赖微管的细胞内运输。正常情况下，KIFs的稳定性对于维持细胞增殖和基因稳态至关重要。然而，KIFs活性异常可能破坏这种动态稳定性，导致细胞分裂失控和肿瘤发生。在这项工作中，我们对KIFs在肝细胞癌和胆管癌发生中的具体作用进行了全面总结，涉及异常信号转导和预后评估潜力。此外，还讨论了KIFs靶向抑制剂目前的临床应用，包括其疗效优势、与药物敏感性或耐药性的关系、联合化疗或其他靶向药物的可行性以及相应的临床试验。总之，异常激活的KIFs通过多种机制参与肿瘤进展的调控，并与肿瘤预后密切相关。同时，针对KIFs的抑制剂也开展了一种有前景的肿瘤靶向治疗策略，值得在肝胆癌（HBC）中进一步研究。
