Targeting CK2 in cancer: a valuable strategy or a waste of time?

Abstract

CK2 is a protein kinase involved in several human diseases (ranging from neurological and cardiovascular diseases to autoimmune disorders, diabetes, and infections, including COVID-19), but its best-known implications are in cancer, where it is considered a pharmacological target. Several CK2 inhibitors are available and clinical trials are underway in different cancer types. Recently, the suitability of CK2 as a broad anticancer target has been questioned by the finding that a newly developed compound, named SGC-CK2-1, which is more selective than any other known CK2 inhibitor, is poorly effective in reducing cell growth in different cancer lines, prompting the conclusion that the anticancer efficacy of CX-4945, the commonly used clinical-grade CK2 inhibitor, is to be attributed to its off-target effects. Here we perform a detailed scrutiny of published studies on CK2 targeting and a more in-depth analysis of the available data on SGC-CK2-1 vs. CX-4945 efficacy, providing a different perspective about the actual reliance of cancer cells on CK2. Collectively taken, our arguments would indicate that the pretended dispensability of CK2 in cancer is far from having been proved and warn against premature conclusions, which could discourage ongoing investigations on a potentially valuable drug target.

Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms

“…Reducing the expression of CK2 subunits with siRNA resulted in a decreased proliferation, survival, migration, and invasiveness in malignant glioma cells and a variety of other cancer cells. Knockout of CK2 with the use of CRISPR technology further confirmed reduced cell proliferation, motility, and invasiveness as a result of CK2 targeting [96].…”

“…Nevertheless, it seems that any reliable conclusions should be withdrawn at this point, considering that the investigation is still ongoing. In addition, recent reports seem to have indicated that other inhibitors under development that are more specific than CX-4945 showed anticancer effect [96].…”

Host kinase CSNK2 is a target for inhibition of pathogenic β-coronaviruses including SARS-CoV-2

“…Use of ATP-competitive kinase inhibitors as chemical probes for target validation in cells can often be confounded by poor selectivity especially at high micromolar doses. For example, it has been proposed that the antiproliferative effects of silmitasertib may result from inhibition of kinases other than CSNK2 (25, 36) due to its modest selectivity. Application of multiple chemogenomic methods can be used to strengthen the association of a cell phenotype with a specific kinase.…”

Inhibition of CK2 Reduces NG2 Expression in Juvenile Angiofibroma

“…Recently, Wells et al [27] suggested SGC-CK2-1 (IC50 = 36 nM) as an efficient CK2 inhibitor [27]. This molecule is considered as non-toxic and, thus, has been proposed to be suitable not only for the treatment of cancers, but also for other pathological conditions, such as neurodegenerative diseases [27,40].…”