# T-type calcium channels regulate medulloblastoma and can be targeted for therapy

## TL;DR

T-type calcium channels are overactive in many medulloblastoma tumors and blocking them with mibefradil can slow tumor growth and improve survival in animal models.

## Contribution

This study is the first to comprehensively analyze T-type calcium channels in medulloblastoma and demonstrate mibefradil as a potential repurposed therapy.

## Key findings

- T-type calcium channels are upregulated in over 30% of medulloblastoma tumors and linked to worse patient outcomes.
- Mibefradil treatment or gene silencing reduced tumor cell growth, viability, and invasion in experiments.
- Mibefradil administration in animal models inhibited tumor growth and extended survival.

## Abstract

The goal of this study was to investigate the role and therapeutic targeting of T-type calcium channels in medulloblastoma, a common and deadly pediatric brain tumor that arises in the cerebellum.

T-type calcium channel expression was assessed in publicly available bulk and single cell RNA-seq datasets. The effects of T-type calcium channel blocker mibefradil on cell growth, death and invasion were assessed with cell counting, alamar blue, trypan blue and transwell assays. Proteomic-based drug target and signaling pathway mapping was performed with Reverse Phase Protein Arrays (RPPA). Co-expression modules of single cell RNA-seq data were generated using high dimensional weighted gene co-expression network analysis (hdWGCNA). Orthotopic xenografts were used for therapeutic studies with the T-Type calcium channel blocker mibefradil.

T-type calcium channels were upregulated in more than 30% of medulloblastoma tumors and patients with high expression associated with a worse prognosis. T-type calcium channels had variable expression across all the subgroups of medulloblastoma at the bulk RNA-seq and single-cell RNA-seq level. Mibefradil treatment or siRNA mediated silencing of T-type calcium channels inhibited tumor cell growth, viability and invasion. RPPA-based protein/phosphoprotein signal pathway activation mapping of T-type calcium channel inhibition and single cell hdWGCNA identified altered cancer signaling pathways. Oral administration of mibefradil inhibited medulloblastoma xenograft growth and prolonged animal survival.

Our results represent a first comprehensive multi-omic characterization of T-type calcium channels in medulloblastoma and provide preclinical data for repurposing mibefradil as a treatment strategy for these relatively common pediatric brain tumors.

The online version contains supplementary material available at 10.1007/s11060-025-04967-5.