Abstract
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.
Highlights
For many decades, much attention has been given to the mechanisms of protein kinases in cellular processes
Among the casein kinase 2 (CK2) inhibitors reviewed here, CX-4945 appears interesting for further research, judging from the preclinical data
This inhibitor exerted an antiproliferative effect verified both in vitro and in vivo, which cannot be said for all CK2 inhibitors
Summary
Much attention has been given to the mechanisms of protein kinases in cellular processes. Chemical compounds that can regulate or inhibit kinases, and prevent diseases, are being sought. These would be specific inhibitors assigned to a particular kinase, in which case the inhibitor would serve as the target of personalized treatment. One of the milestones in cancer treatment turned out to be the chemical inhibition of protein kinases and the use of kinase inhibitors in the fight against cancer. The discovery of imatinib changed the approach to treatment and at the same time started the expansion of kinase inhibitors as a new class of drugs [4].
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