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A small study has shown that an old heart drug known as digoxin may help slow the spread of tumors to other organs by breaking up clumps of cancer cells.
However, the research is in its early stages, so it will take time to determine whether it will be effective in treating cancer, including breast cancer, the scientists say.
Breast cancer is one of the leading causes of cancer death among women in the United States, largely due to its ability to metastasize from the breast to other parts of the body. These migrating cancer cells can invade vital organs such as the brain or lungs, making treatment difficult. Standard cancer therapies aim to kill tumor cells but are not specifically designed to stop metastasis.
Circulating tumor cells—cancer cells that break away from tumors and enter the bloodstream—play a key role in the metastasis process. These cells are more likely to form new tumors in other parts of the body when they gather in groups rather than when they travel alone.
Recent research in Switzerland has identified existing drugs that may help disrupt these clusters. Experiments in mice have shown that the drugs reduce the spread of breast cancer, suggesting a new approach to limiting metastasis. The drugs, known as Na+/K+ ATPase inhibitors, include digoxin and work by altering the flow of charged particles in and out of cells.
Building on their previous research, the scientists have now conducted a clinical trial to test whether digoxin can reduce circulating tumor cell clusters in women with metastatic breast cancer. Based on early results published Jan. 24 in the journal Nature Medicine, the researchers suggest that digoxin could one day complement other treatments that target primary tumors, or cancers that have not yet spread.
First study of digoxin in human cancer
Digoxin is an old drug that was first isolated from the foxglove plant (Digitalis lanata) in 1930. It is used to treat heart failure and atrial fibrillation and works by blocking structures in heart cells called sodium-potassium pumps, which regulate sodium and potassium levels inside cells. Blocking the pumps with digoxin results in stronger contractions and a slower heart rate.
Scientists now suggest that the effect of digoxin could be used in cancer treatment.
By inhibiting sodium-potassium pumps in tumor cells, digoxin promotes the cells’ increased uptake of calcium. Previous studies have shown that elevated calcium levels in cells can disrupt the formation of tight junctions and desmosomes, structures that hold cells together. Digoxin thus appears to weaken the connections between cancer cells, causing them to break apart.
The team observed these effects in mice. To test whether digoxin could also disrupt tumor cell clusters in patients, they recruited nine women with metastatic breast cancer. Each participant had at least one circulating tumor cell cluster at the time of screening.
In the study, women took digoxin daily for seven days. To track circulating tumor cells, researchers took blood samples from the participants before treatment, two hours after the first doses, and again three and seven days into the study.
The researchers noted that the average size of the cancer cell clusters in the participants decreased by 2.2 cells per cluster after treatment. The average cluster contained four cells before treatment. There were no serious side effects from the therapy.
Questions to answer
Although the trial results are promising, they have some limitations.
Dr. Daniel Smith and Dr. Klaus Pantel of the University Medical Center Hamburg-Eppendorf in Germany noted in a commentary on the new study that the reduction
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