TOPK:值得关注的肺癌治疗靶点

Wenbo Liu, Feng Zhu, Q. Duan, Yafang Li, Shuang Zhao, Juanjuan Xiao, Yijie Zhang
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摘要

T-LAK细胞源性蛋白激酶(TOPK)是一种丝氨酸/苏氨酸蛋白激酶,特异性表达于活跃增殖的细胞,如正常睾丸生殖细胞、淋巴细胞和各种肿瘤细胞。它在细胞生长、转移、耐药性、血管生成和炎症等多个生物过程中发挥着关键作用,是一个很有前景的肿瘤治疗靶点。在肺癌中已观察到 TOPK 的异常过表达或激活,这与肺癌的发生、发展、临床结果和不良预后有关。抑制 TOPK 对减少肿瘤生长具有显著的治疗潜力,甚至可以与化疗或放疗联合使用。因此,以 TOPK 为靶点为肺癌的预防和治疗提供了一条前景广阔的途径。本文综述了TOPK在肺癌发生、发展和耐药性中的作用,总结了肺癌中受TOPK影响的主要信号通路,并分析了其治疗价值。文章还讨论了 TOPK 在肺癌靶向治疗、化疗、放疗和免疫治疗中的作用和潜力。此外,还总结了使用 TOPK 抑制剂治疗肺癌的最新进展,并讨论了其未来的临床应用。总之,TOPK 是治疗肺癌的重要靶点,进一步开发特异性 TOPK 抑制剂对于肺癌的综合治疗不可或缺。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TOPK: A noteworthy target for lung cancer treatment
T-LAK cell-originated protein kinase (TOPK) is a serine/threonine protein kinase that is specifically expressed in actively proliferating cells, such as normal testicular germ cells, lymphocytes, and various tumor cells. It plays a key role in multiple biological processes, such as cell growth, metastasis, drug resistance, angiogenesis, and inflammation, and is a promising therapeutic target for tumors. Aberrant TOPK overexpression or activation has been observed in lung cancer and is related to lung cancer occurrence and development, clinical outcome, and poor prognosis. The inhibition of TOPK has demonstrated significant therapeutic potential for reducing tumor growth and can even be used in combination with chemotherapy or radiotherapy. Thus, targeting TOPK provides a promising avenue for the prevention and treatment of lung cancer. This article reviews the role of TOPK in the occurrence, development, and drug resistance of lung cancer; summarizes the main signaling pathways affected by TOPK in lung cancer; and analyzes its therapeutic value. The role and potential of TOPK in targeted therapy, chemotherapy, radiotherapy, and immunotherapy for lung cancer are also discussed. In addition, the latest progress in the use of TOPK inhibitors for lung cancer treatment is summarized, and their future clinical application is discussed. Overall, TOPK is a valuable target for the treatment of lung cancer, and further development of specific TOPK inhibitors is indispensable for the comprehensive treatment of lung cancer.
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