Repurposing an arrhythmia drug to fend off breast cancer metastasis: animal study

There are no approved treatments for the process of metastasis, in which cancerous tumors spread to additional sites in the body. Now, researchers say repurposing an FDA-approved med for irregular heartbeat might help.

A team of researchers at Tufts University found that using ion channel blockers significantly limited tumor cell invasion in a lab dish and reduced metastasis in an animal model of breast cancer. The findings were published this month in eBioMedicine.

The meds helped manipulate voltage patterns in the tumor cells. Unlike normal cells, tumor cells undergo a breakdown in electrical voltage patterns. They no longer behave like normal cells in that location of the body, which allows them to expand into other tissues.

Ion channels regulate the cell's bioelectrical properties. Given that they are the second-most common target for marketed meds, researchers have a "relatively large set of ready-to-use drugs" that they could repurpose as cancer therapies, Madeleine Oudin, Ph.D., assistant professor of biomedical engineering at Tufts, said in a statement

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The researchers looked at triple-negative breast cancer, or TNBC, because it has the greatest likelihood of metastasis among all subtypes of breast cancer. The subtype comprises 15% of breast cancer cases and has a five-year prognosis of 77% overall, but just 12% after it's metastasized, according to the American Cancer Society.

In an animal study, the repurposed meds were able to shrink the number of metastatic sites in mouse lungs by half. The researchers blocked the potassium ion channels to help restore voltage in the cells to more normal levels, which helped reduce the tumor cell invasion and metastasis. 

Of four approved potassium ion channel blockers that were screened, amiodarone had the biggest impact on normalizing cell voltages. The drug is used to treat heart rhythm disorders and was able to specifically target cells that break off from the primary tumor. 

Because amiodarone is already on the market for other conditions, phase 1 clinical trials "could commence in the near future," the Tufts team said. Lead study author Samantha Payne said the drug could be combined with existing chemotherapies. 

Metastasis has been the target of other recent developments. A Mount Sinai team found that dormant metastatic cells wake up when certain collagen protein levels wear off. The researchers suggest their findings could help predict cancer metastasis and recurrence. Elsewhere, University of California researchers published a map of protein-protein interactions that fuel metastasis in cancer in the hopes it will lead to new treatment options.