Tulane University School of Medicine, Department of Pharmacology, New Orleans LA, United States.
Structural Genomics Consortium and the Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Curr Med Chem. 2021;28(30):6096-6109. doi: 10.2174/0929867328666210322101749.
Mitotic kinases have integral roles in cell processes responsible for cancer development and progression in all tumor types and are common targets for therapeutics. However, a large subset of the human kinome remains unexplored with respect to functionality in cancer systems. Within the mitotic kinases, the never-in-mitosis kinase (NEK) family is emerging as novel kinase targets in various cancer types. NEK5 is an understudied member of the NEK family. While there are more recent studies describing the physiologic function of NEK5, its role in cancer biology remains widely understudied. However, emerging studies implicate that NEK5 has potentially crucial functions in various solid tumors. In this review, we discuss current knowledge regarding the role of NEK5 in cancer and the implications of NEK5 expression and activity in tumor development and metastasis. We summarize current studies that examine NEK5 activity in diverse cancer systems and cellular processes. As an understudied kinase, there are currently no selective NEK5-targeting agents to test the effects of pharmacologic inhibition on cancer, although there exist recent advancements in this area. Here we also include an update on efforts to develop selective pharmacologic inhibition of NEK5, and we discuss the current direction of NEK5-targeting therapeutic development. The generation of selective NEK5 inhibitors is promising new targeted therapies for cancer growth and metastasis.
有丝分裂激酶在所有肿瘤类型的癌症发生和发展过程中起着至关重要的作用，是治疗的常见靶点。然而，人类激酶组的很大一部分在癌症系统中的功能仍未得到探索。在有丝分裂激酶中，从不进入有丝分裂的激酶 (NEK) 家族在各种癌症类型中作为新型激酶靶点出现。NEK5 是 NEK 家族中研究较少的成员。虽然最近有研究描述了 NEK5 的生理功能，但它在癌症生物学中的作用仍未得到广泛研究。然而，新出现的研究表明 NEK5 在各种实体瘤中具有潜在的关键功能。在这篇综述中，我们讨论了目前关于 NEK5 在癌症中的作用的知识，以及 NEK5 表达和活性在肿瘤发生和转移中的意义。我们总结了目前研究中检查不同癌症系统和细胞过程中 NEK5 活性的研究。作为一个研究较少的激酶，目前还没有专门针对 NEK5 的靶向药物来测试对癌症的药理抑制作用，尽管在这一领域最近有了一些进展。在这里，我们还介绍了开发选择性 NEK5 药理抑制的最新进展，并讨论了目前针对 NEK5 的治疗开发方向。生成选择性 NEK5 抑制剂为癌症的生长和转移提供了有前途的新靶向治疗方法。
