Cancer Bioelectricity

Where things stand

Cancer cells often have a more depolarized resting membrane potential than the healthy cells they came from, and many tumours abnormally express ion channels. A notable example is the neonatal form of the sodium channel Nav1.5 in metastatic breast cancer, which has been linked to invasiveness. This line of work suggests ion channels as both biomarkers and drug targets.

In the clinic

The clearest clinical application is physical rather than pharmacological. Tumor Treating Fields apply alternating electric fields through skin electrodes. Novocure's Optune device was FDA-approved for recurrent glioblastoma in 2011 and newly diagnosed glioblastoma in 2015, and the approach has since extended to mesothelioma and, in 2024, metastatic non-small cell lung cancer.

Cancer neuroscience

In 2019 two groups reported in Nature that glioma cells form functional synapses with neurons, and that neuronal activity drives tumour growth (Venkatesh et al.; Venkataramani et al.). This made electrical signalling between nerves and tumours a target in its own right.

What is contested

The mechanism of Tumor Treating Fields is still debated, and their benefit has been questioned because trials could not be blinded. Most evidence that repurposed ion-channel drugs slow metastasis comes from cell and animal studies or retrospective analyses, not randomized trials.

What to watch

Randomized trials of channel-blocking drugs, results from neuron–tumour synapse inhibitors, and new Tumor Treating Fields indications.