Park Jae-Hyun, Chung Suyoun, Matsuo Yo, Nakamura Yusuke
Department of Medicine , The University of Chicago , 900 E 57th street KCBD 6130 , Chicago , IL 60637 , USA . Email:
OncoTherapy Science, Inc. , Kawasaki , 213-0012 , Japan.
Medchemcomm. 2016 Nov 11;8(1):73-80. doi: 10.1039/c6md00385k. eCollection 2017 Jan 1.
Cancer stem cells (CSCs) are indicated to play critical roles in drug resistance, recurrence, and metastasis of cancer. Although molecular targeted therapies have contributed to the improvement of cancer treatments by targeting vulnerable pathways indispensable to the proliferation and survival of cancer cells, no relevant therapeutic modalities targeting CSCs have been developed yet. This review focuses on MELK (maternal embryonic leucine zipper kinase), TOPK (T-lymphokine-activated killer cell-originated protein kinase), and TTK (tyrosine threonine kinase), which are over-expressed frequently in human cancers and play indispensable roles in the development and maintenance of cancer stem cells. In addition, we will discuss recently developed small molecules for these protein targets, which have shown remarkable anti-tumor efficacies in several preclinical studies.
癌症干细胞（CSCs）被认为在癌症的耐药性、复发和转移中起关键作用。尽管分子靶向疗法通过靶向癌细胞增殖和存活所必需的脆弱途径，为癌症治疗的改善做出了贡献，但尚未开发出针对癌症干细胞的相关治疗方法。本综述重点关注母源胚胎亮氨酸拉链激酶（MELK）、T淋巴细胞激活的杀伤细胞起源蛋白激酶（TOPK）和酪氨酸苏氨酸激酶（TTK），它们在人类癌症中经常过度表达，并在癌症干细胞的发育和维持中发挥不可或缺的作用。此外，我们将讨论最近针对这些蛋白质靶点开发的小分子，这些小分子在几项临床前研究中显示出显著的抗肿瘤疗效。
