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Capturing the Interaction Kinetics of an Ion Channel Protein with Small Molecules by the Bio-layer Interferometry Assay
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EAG2 potassium channel with evolutionarily conserved function as a brain tumor target

Xi Huang1,2, Ye He1,2, Adrian M Dubuc3

  • 1Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, San Francisco, California, USA.

Nature Neuroscience
|August 11, 2015
PubMed

Insights

Scientists discovered the EAG2 potassium channel drives brain tumor growth and metastasis. An existing drug, thioridazine, blocks this channel, reducing tumor progression in preclinical models and a human patient.

Area of Science:

  • Oncology
  • Neuroscience
  • Molecular Biology

Background:

  • Ion channels are crucial drug targets, yet none are FDA-approved for cancer.
  • The EAG2 potassium channel's role in cancer, particularly brain tumors, is largely unexplored.

Observation:

  • EAG2 potassium channel is essential for brain tumor growth and metastasis.
  • EAG2 localizes to the trailing edge of migrating medulloblastoma cells, influencing cell volume and motility.

Findings:

  • EAG2 potassium channel functionally cooperates with other potassium channels to regulate cell volume during mitosis and tumor progression.
  • The FDA-approved drug thioridazine effectively blocks EAG2 channels, inhibiting medulloblastoma growth and metastasis in preclinical models.
  • A case study demonstrates thioridazine's potential in treating a human patient with medulloblastoma.

Implications:

  • Targeting the EAG2 potassium channel represents a novel therapeutic strategy for brain cancers.
  • Drug repurposing of thioridazine offers a potential new treatment avenue for medulloblastoma.
  • This research highlights the broader potential of targeting ion channels in cancer therapy.

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