Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant risk of metastasis. Like many cancers, it comes in multiple molecularly defined subgroups. While clinical trials are under way with drugs that treat a quarter of cases that are represented by one molecular subgroup (Sonic hedgehog), targets for drugs have not been identified for the remaining cases. But in a recent paper in Nature Neuroscience (doi:10.1038/nn.4088; published online 10 August 2015, Lily Jan (University of San Francisco) and colleagues showed that a drug targeting a potassium channel was effective in reducing medulloblastoma growth in mice.

Previous work from the Jan group had shown that the voltage-gated potassium channel, EAG2, was more abundant in medulloblastoma cells. Now the authors have shown that mutating the Drosophila homolog, EAG, impaired tumor growth in three different brain tumor models. Curious whether this effect was specific to EAG2, they used gene expression profiling of human medulloblastoma and cells from fly tumors to identify other ion channels whose expression was altered. This allowed them to identify another potassium channel, KCNT2, whose expression is increased in various cancers. Inhibiting expression or activity of KCNT2 also impaired medulloblastoma growth in vitro. Further experiments in medulloblastoma cells showed that both channels regulate cell volume and motility, thus affecting cell growth.

To test whether their findings might have clinical potential, the authors tested several drugs already approved by the FDA to determine whether they might inhibit EAG2 activity and prevent medulloblastoma growth. This screen identified the antipsychotic drug thioridazine. When given to mice with human medulloblastoma cells, thioridazine caused tumor regression.

More than one-fifth of drugs used to treat human diseases target ion channels, but this study is the first to show that such drugs might effectively treat cancer. Further work is needed to determine whether these findings will translate to humans. It is also exciting that an FDA-approved drug could be repurposed to treat cancer, although thioridazine has significant side effects. “The development of a drug designed to act on this newly identified target more specifically and more powerfully, with fewer side effects, would have the potential to improve outcomes for many with this disease,” said Jan in a press release. “Targeting of ion channels in cancer is a new frontier, and will be exciting to further explore as a way both to stop the growth of tumors and to limit their potential to spread.”