# Switching off CK2-mediated activation of survivin offers new therapeutic opportunities in neuroblastoma

## TL;DR

A new CK2 inhibitor called CK2-TN03 shows promise in treating neuroblastoma by reducing cancer cell growth and survivin activity.

## Contribution

CK2-TN03 is a novel CK2 inhibitor with greater selectivity and efficacy than existing inhibitors for neuroblastoma treatment.

## Key findings

- CK2-TN03 significantly reduces neuroblastoma growth in vitro and in vivo.
- CK2-TN03 suppresses survivin by inhibiting its phosphorylation and reducing its mRNA and protein levels.
- CK2-TN03 induces mitotic arrest and apoptosis in neuroblastoma cells without affecting noncycling cells.

## Abstract

CK2 is an antiapoptotic kinase overactive in various malignancies. Here we show that CK2 inhibition dramatically affects neuroblastoma growth both in vitro and in vivo. In particular, here we report on the identification of CK2-TN03, a CK2 inhibitor showing greater selectivity and cellular efficacy than silmitasertib, the only available clinical grade CK2 inhibitor with orphan status for cholangiocarcinoma and in clinical trials for medulloblastoma. CK2-TN03 acts by suppressing survivin, which is overexpressed in all high-risk neuroblastomas. Survivin function is affected by direct inhibition of its phosphorylation by CK2; its messenger RNA and protein levels are reduced through CK2 regulation of the MDM2/p53 balance via AKT1 and BRD4/MYCN. Accordingly, neuroblastoma cells persistently stall in mitosis before going to apoptosis. Finally, CK2-TN03 does not affect noncycling cells and significantly reduces tumor growth in mice xenografts without any apparent toxicity.

Researchers have been exploring ways to inhibit CK2 to treat cancers such as neuroblastoma, a type of cancer that affects nerve cells. The study addresses the challenge of finding effective CK2 inhibitors. Researchers identified a new CK2 inhibitor called CK2-TN03. They tested its effects on various cancer cell lines, including neuroblastoma cells, using laboratory experiments. The study involved testing the compound’s ability to reduce cancer cell growth and induce cell death. They also examined how CK2-TN03 affects proteins involved in cell division and survival. Results showed CK2-TN03 effectively reduced tumor growth in neuroblastoma cells and was more potent than an existing inhibitor, CX-4945. It worked by disrupting the function of a protein called survivin, which helps cancer cells survive and divide. Researchers concluded that CK2-TN03 has potential as a treatment for neuroblastoma and possibly other cancers.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.