Chua Melissa M J, Ortega Charina E, Sheikh Ayesha, Lee Migi, Abdul-Rassoul Hussein, Hartshorn Kevan L, Dominguez Isabel
Department of Medicine, School of Medicine, Boston University, Boston, MA 02118, USA.
Pharmaceuticals (Basel). 2017 Jan 28;10(1):18. doi: 10.3390/ph10010018.
CK2 genes are overexpressed in many human cancers, and most often overexpression is associated with worse prognosis. Site-specific expression in mice leads to cancer development (e.g., breast, lymphoma) indicating the oncogenic nature of CK2. CK2 is involved in many key aspects of cancer including inhibition of apoptosis, modulation of signaling pathways, DNA damage response, and cell cycle regulation. A number of CK2 inhibitors are now available and have been shown to have activity against various cancers in vitro and in pre-clinical models. Some of these inhibitors are now undergoing exploration in clinical trials as well. In this review, we will examine some of the major cancers in which CK2 inhibition has promise based on in vitro and pre-clinical studies, the proposed cellular and signaling mechanisms of anti-cancer activity by CK2 inhibitors, and the current or recent clinical trials using CK2 inhibitors.
CK2基因在许多人类癌症中过度表达,而且大多数情况下,过度表达与较差的预后相关。在小鼠中的位点特异性表达会导致癌症发生(如乳腺癌、淋巴瘤),这表明CK2具有致癌性。CK2参与癌症的许多关键方面,包括抑制细胞凋亡、调节信号通路、DNA损伤反应和细胞周期调控。现在有多种CK2抑制剂,并且已证明它们在体外和临床前模型中对各种癌症具有活性。其中一些抑制剂目前也正在进行临床试验探索。在本综述中,我们将基于体外和临床前研究,探讨CK2抑制有望发挥作用的一些主要癌症、CK2抑制剂抗癌活性的推测细胞和信号机制,以及目前或近期使用CK2抑制剂的临床试验。