Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics.
Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics.
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DOI：
10.1158/1535-7163.mct-15-0897
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发表时间：
2016-07
影响因子：
5.7
通讯作者：
Ahmad N
中科院分区：
文献类型：
--
作者：
Gutteridge RE;Ndiaye MA;Liu X;Ahmad N
Polo样激酶1（Plk 1）过表达已被证明发生在广泛的肿瘤中，促进了Plk 1抑制剂作为癌症治疗手段的研究和开发。本文综述了Plk 1抑制剂在癌症治疗中的最新进展。Plk 1抑制已显示导致具有较高有丝分裂指数的细胞的有丝分裂阻滞和凋亡，因此Plk 1表达较高。Plk 1抑制剂作为癌症治疗剂的潜力已被广泛研究。然而，对Plk 1生物学/机制的完整理解尚未完全实现。对某些化疗药物的抗性与Plk 1过表达有关，并且已经发现Plk 1介导的有丝分裂事件如微管重排会降低化疗药物的疗效。Plk 1抑制剂volasertib在临床研究中显示出相当大的前景，已进入III期试验。然而，Plk 1抑制剂的临床前成功并没有很好地转化为临床成功。在我们看来，靶向其他相关途径与Plk 1的联合治疗对于解决单药治疗观察到的问题，特别是耐药性至关重要。此外，研究还应致力于了解Plk 1的机制，并设计新一代特异性、有效的Plk 1抑制剂来靶向癌症。
Polo-like kinase 1 (Plk1) overexpression has been shown to occur in a wide range of tumors, prompting research and development of Plk1 inhibitors as a means of cancer treatment. This review discusses recent advances in the development of Plk1 inhibitors for cancer management. Plk1 inhibition has been shown to cause mitotic block and apoptosis of cells with higher mitotic index and therefore higher Plk1 expression. The potential of Plk1 inhibitors as cancer therapeutics has been widely investigated. However, a complete understanding of Plk1 biology/mechanism is yet to be fully achieved. Resistance to certain chemotherapeutic drugs has been linked to Plk1 overexpression, and Plk1-mediated mitotic events such as microtubule rearrangement have been found to reduce the efficacy of chemotherapeutic agents. The Plk1 inhibitor, volasertib, has shown considerable promise in clinical studies, having reached phase III trials. However, preclinical success with Plk1 inhibitors has not translated well into clinical success. In our view, combined therapies targeting other relevant pathways together with Plk1 may be vital to combat issues observed with monotherapy, especially resistance. In addition, research should also be directed towards understanding the mechanisms of Plk1 and designing additional next generations of specific, potent Plk1 inhibitors to target cancer.