The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies.
The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies.
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DOI：
10.3389/fphar.2015.00070
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发表时间：
2015
影响因子：
5.6
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Chon HJ;Bae KJ;Lee Y;Kim J
酪蛋白激酶2（CK 2）蛋白激酶是一种促存活激酶，是治疗多种人类癌症的治疗靶点。CK 2过表达已在血液恶性肿瘤中得到证实，包括慢性淋巴细胞性白血病、慢性髓性白血病、急性成淋巴细胞性白血病、急性髓性白血病和多发性骨髓瘤。CX-4945，也称为Silmitasertib，是一种口服给药的高度特异性CK 2 ATP竞争性抑制剂。CX-4945诱导细胞毒性和细胞凋亡，目前正在临床试验中评估其治疗多种癌症类型。在过去的2年中，CX-4945的治疗潜力的重点已经从实体瘤转移到血液恶性肿瘤。CX-4945通过下调CK 2表达和抑制CK 2介导的PI 3 K/Akt/mTOR信号通路的激活，在血液肿瘤中发挥抗增殖作用。此外，CX-4945与其他抑制剂的组合在细胞死亡诱导中产生协同效应。这些新发现表明，CK 2过表达有助于血液癌细胞存活和对化疗的抵抗。CX-4945的组合使用是治疗血液恶性肿瘤的有前景的治疗工具。
The casein kinase 2 (CK2) protein kinase is a pro-survival kinase and therapeutic target in treatment of various human cancers. CK2 overexpression has been demonstrated in hematological malignancies, including chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and multiple myeloma. CX-4945, also known as Silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2. CX-4945 induces cytotoxicity and apoptosis and is currently being evaluated in clinical trials for treatment of many cancer types. In the past 2 years, the focus on the therapeutic potential of CX-4945 has shifted from solid tumors to hematological malignancies. CX-4945 exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways. Furthermore, combination of CX-4945 with other inhibitors yielded synergistic effects in cell death induction. These new findings demonstrate that CK2 overexpression contributes to blood cancer cell survival and resistance to chemotherapy. Combinatorial use of CX-4945 is a promising therapeutic tool for treatment of hematological malignancies.
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