Successful trials in breast cancer patients reveal that digoxin, a medication typically used for heart conditions, has the ability to break up groups of circulating breast cancer cells in the bloodstream, thereby lowering the chance of metastasis formation.
Certain types of tumors can move from their original site and spread throughout the body, creating metastases. This occurs because the primary tumor continuously releases cancer cells into the circulatory system. These circulating tumor cells (CTCs) can cluster together, forming small groups of up to a dozen cells, which may settle in other organs. Once there, these clusters can grow into larger tumors known as metastases. Metastatic tumors remain a significant medical challenge, with approximately seven million individuals worldwide succumbing to them each year.
Breast cancer serves as a notable example of a tumor that can spread. Once the primary tumor begins to metastasize, the likelihood of survival sharply declines, leading to the deaths of tens of thousands of women globally each year. Oncologists are actively seeking methods to diminish or eliminate these clusters to hinder metastasis formation.
Substantial reduction in metastasis risk
A recent clinical study published in the journal Nature Medicine presents a promising new strategy. A research team from ETH Zurich, along with University Hospitals of Basel and Zurich, and the Basel-Land Cantonal Hospital, administered low and safe doses of digoxin for one week to nine breast cancer patients with metastasis.
The outcome was a significant reduction in the number of cells per cluster, averaging a decrease of 2.2 cells. Considering that these clusters usually comprise only a few cells, this finding suggests a substantial lowering of metastasis risk. Smaller clusters are less likely to successfully lead to metastases. “Breast cancer metastasis relies on CTC clusters,” says principal investigator Nicola Aceto, a Professor of Molecular Oncology at ETH Zurich. “The larger the clusters, the more likely they are to succeed.”
The vulnerability of CTC clusters lies in the sodium-potassium pumps (Na+/K+-ATPases) found in the membranes of cancer cells. These pumps are responsible for moving sodium out of cells and bringing potassium in. Digoxin interferes with these ion pumps, disrupting the exchange process. As a result, the cells absorb more calcium, weakening the bonds among the cancer cells within the cluster, which leads to their disintegration.
However, it’s important to note that digoxin alone is not capable of eradicating existing tumors. For that, it must be used alongside other treatments that can eliminate the cancer cells already present.
Researchers aim to enhance the active ingredient
Digoxin is derived from the foxglove plant (Digitalis sp.) and is commonly prescribed for heart-related issues such as heart failure. The researchers at ETH discovered in 2019 that digoxin might also have potential in treating breast cancer. They conducted a thorough screening, testing over 2,400 different substances in cell cultures to identify effective agents against CTC clusters.
Moving forward, the researchers plan to create new compounds based on digoxin that will more effectively dissolve CTC clusters. The ETH spin-off, Page Therapeutics, is currently working on this development.
Aceto also intends to extend his studies to other cancer types known for spreading, including prostate, colorectal, and pancreatic cancers, as well as melanoma. Initial laboratory experiments have already commenced.
This study exemplifies exemplary collaboration between ETH Zurich and several hospitals, including the University Hospitals of Basel and Zurich, as well as the Basel-Land Cantonal Hospital, where the patient recruitment and clinical trials took place.
