Pucko Emanuela B, Ostrowski Robert P
Department of Experimental and Clinical Neuropathology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego St., 02-106 Warsaw, Poland.
Pharmaceutics. 2022 Jan 30;14(2):331. doi: 10.3390/pharmaceutics14020331.
In gliomas, casein kinase 2 (CK2) plays a dominant role in cell survival and tumour invasiveness and is upregulated in many brain tumours. Among CK2 inhibitors, benzimidazole and isothiourea derivatives hold a dominant position. While targeting glioma tumour cells, they show limited toxicity towards normal cells. Research in recent years has shown that these compounds can be suitable as components of combined therapies with hyperbaric oxygenation. Such a combination increases the susceptibility of glioma tumour cells to cell death via apoptosis. Moreover, researchers planning on using any other antiglioma investigational pharmaceutics may want to consider using these agents in combination with CK2 inhibitors. However, different compounds are not equally effective when in such combination. More research is needed to elucidate the mechanism of treatment and optimize the treatment regimen. In addition, the role of CK2 in gliomagenesis and maintenance seems to have been challenged recently, as some compounds structurally similar to CK2 inhibitors do not inhibit CK2 while still being effective at reducing glioma viability and invasion. Furthermore, some newly developed inhibitors specific for CK2 do not appear to have strong anticancer properties. Further experimental and clinical studies of these inhibitors and combined therapies are warranted.
在胶质瘤中,酪蛋白激酶2(CK2)在细胞存活和肿瘤侵袭中起主导作用,并且在许多脑肿瘤中上调。在CK2抑制剂中,苯并咪唑和异硫脲衍生物占据主导地位。在靶向胶质瘤肿瘤细胞时,它们对正常细胞显示出有限的毒性。近年来的研究表明,这些化合物可作为高压氧联合治疗的组成部分。这种联合增加了胶质瘤肿瘤细胞对凋亡导致的细胞死亡的敏感性。此外,计划使用任何其他抗胶质瘤研究药物的研究人员可能希望考虑将这些药物与CK2抑制剂联合使用。然而,不同化合物在这种联合使用时效果并不相同。需要更多研究来阐明治疗机制并优化治疗方案。此外,CK2在胶质瘤发生和维持中的作用最近似乎受到了挑战,因为一些结构与CK2抑制剂相似的化合物并不抑制CK2,但仍能有效降低胶质瘤的活力和侵袭性。此外,一些新开发的CK2特异性抑制剂似乎没有很强的抗癌特性。有必要对这些抑制剂和联合疗法进行进一步的实验和临床研究。