Gowda Chandrika, Sachdev Mansi, Muthusami Sunil, Kapadia Malika, Petrovic-Dovat Lidija, Hartman Melanie, Ding Yali, Song Chunhua, Payne Jonathon L, Tan Bi-Hua, Dovat Sinisa
Department of Pediatrics, H085, Division of Pediatric Hematology/Oncology, 500 University Drive, P.O. Box 850, Hershey, Pennsylvania 17033-0850. United States.
Curr Pharm Des. 2017;23(1):95-107. doi: 10.2174/1381612822666161006154311.
Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies including breast, prostate, and lung cancer are being tested. Although many CK2 inhibitors exist, only a few have emerged as selective inhibitors that are potent and effective. CX-4945 is a selective, orallybioavailable small molecule inhibitor, which has shown encouraging results in pre-clinical models of leukemia.
In this review we will elaborate on the structure and physiological function of the CK2 protein as well as its role in cancer. We will review, in depth, the role of CK2 in leukemia and its mechanisms of tumorigenesis via phosphorylation of the tumor suppressor protein Ikaros. We will discuss both the importance of Ikaros in leukemia suppression and the restoration of Ikaros' tumor suppressor function after CK2 inhibition by CX-4945 (a CK2-specific inhibitor).
CK2 is an oncogene that is overexpressed in hematological malignancies. In high risk Pre-B ALL, CK2 phosphorylates Ikaros tumor suppressor and promotes leukemogenesis. Inhibition of CK2 using CX4945 restores Ikaros function and leads to anti leukemic effects in vitro and in pre-clinical leukemia models.
CK2 is an attractive target in treatment of various cancers. Currently only a few specific CK2 inhibitors are available. Preclinical studies using CK2 inhibitor, CX4945 in high risk pediatric leukemias have shown promising results and warrants further testing in other types of leukemia.
酪蛋白激酶II（CK2）是一种促癌蛋白，正逐渐成为癌症治疗中一个有前景的靶点。最近的研究揭示了CK2在肿瘤发生中的重要作用。在包括白血病在内的许多恶性肿瘤中都发现CK2水平较高。目前正在测试CK2抑制剂在包括乳腺癌、前列腺癌和肺癌在内的各种恶性肿瘤中的应用。尽管存在许多CK2抑制剂，但只有少数几种成为了有效且有选择性的抑制剂。CX-4945是一种选择性、口服生物可利用的小分子抑制剂，在白血病的临床前模型中已显示出令人鼓舞的结果。
在本综述中，我们将详细阐述CK2蛋白的结构和生理功能及其在癌症中的作用。我们将深入回顾CK2在白血病中的作用及其通过磷酸化肿瘤抑制蛋白伊卡罗斯（Ikaros）的肿瘤发生机制。我们将讨论伊卡罗斯在白血病抑制中的重要性以及在CX-4945（一种CK2特异性抑制剂）抑制CK2后伊卡罗斯肿瘤抑制功能的恢复。
CK2是一种在血液系统恶性肿瘤中过度表达的癌基因。在高危前B细胞急性淋巴细胞白血病中，CK2使肿瘤抑制蛋白伊卡罗斯磷酸化并促进白血病发生。使用CX4945抑制CK2可恢复伊卡罗斯功能，并在体外和临床前白血病模型中产生抗白血病作用。
CK2是治疗各种癌症的一个有吸引力的靶点。目前仅有少数几种特异性CK2抑制剂。使用CK2抑制剂CX4945对高危儿童白血病进行的临床前研究已显示出有前景的结果，值得在其他类型白血病中进一步测试。
