A recent study published in Nature Medicine reveals that digoxin, a drug traditionally used for heart conditions, can significantly reduce the size of circulating tumor cell (CTC) clusters in patients with metastatic breast cancer. This finding offers a promising avenue for preventing cancer metastasis, a major cause of cancer-related deaths worldwide.
The clinical trial, conducted by researchers from ETH Zurich, the University Hospitals of Basel and Zurich, and the Basel-Land Cantonal Hospital, involved administering a low, safe dosage of digoxin to nine patients with metastatic breast cancer for one week. The results showed a significant decrease in the number of cells per CTC cluster, averaging a reduction of 2.2 cells. Given that typical cluster sizes are small, this reduction is considered clinically significant in lowering the risk of metastasis.
Mechanism of Action
The researchers identified the sodium-potassium pumps (Na+/K+-ATPases) on tumor cell membranes as the Achilles' heel of CTC clusters. Digoxin functions by blocking these ion pumps, disrupting the exchange of sodium and potassium. This disruption leads to an increase in intracellular calcium, weakening the connections between cancer cells within the cluster and causing them to break apart.
Professor Nicola Aceto, Professor of Molecular Oncology at ETH Zurich, explained, "Breast cancer metastasis depends on CTC clusters. The larger they are, the more successful they are." The study highlights that by reducing cluster size, digoxin can potentially hinder the metastatic process.
Clinical Implications and Future Directions
While digoxin alone cannot eliminate existing tumors, its ability to disrupt CTC clusters suggests it could be a valuable addition to combination therapies. The researchers emphasize that digoxin would need to be administered alongside other agents that target and kill existing cancer cells.
Building on these findings, the researchers are now focused on developing novel molecules based on digoxin that are even more effective at dissolving CTC clusters. Page Therapeutics, an ETH spin-off, is actively working on this endeavor. Furthermore, Professor Aceto plans to expand the research to other cancer types known to metastasize, including prostate, colorectal, pancreatic cancer, and melanoma.
Angle PLC's Parsortix system played a key role in this research, enabling the identification of patients with highly metastatic CTC clusters. This allowed researchers to select patients most likely to benefit from digoxin treatment. Karen Miller, Angle's chief scientific officer, stated that the Parsortix system's unique design and ability to capture CTC clusters will be crucial for developing drugs targeting the metastatic cascade.
The study represents a significant step forward in understanding and potentially preventing cancer metastasis. By targeting CTC clusters, researchers hope to develop more effective strategies to improve outcomes for patients with metastatic cancer.
