The number of cancer cells per cluster decreased significantly – by an average of 2.2 cells. That is meaningful because typical cluster sizes are only a handful of cells, which could lead to a significant reduction in the risk of metastases. Breast cancer is an example of a tumor that spreads by releasing cancer cells into the blood. These circulating tumor cells join together into small clusters of up to a dozen cells and settle in other organs., where they grow into larger tumors - metastases. Metastatic tumors caused around seven million deaths each year.
Digoxin probably works because ot blocks the sodium-potassium pumps which are located in the membranes of tumor cells and are responsible for transporting sodium out of the cells and potassium into them. By suppressing that ion exchange, cells absorb more calcium from the outside of the cell membrane which weakens the cohesion of the cancer cells in the cluster, causing them to fall apart.

a, Study flow chart. b, Representative images of a single CTC and homotypic and heterotypic CTC clusters (scale bar, 10 µm), stained with EpCAM, HER2 and EGFR (green) and CD45 (magenta). c,d, LME random coefficients showing a negative association between treatment and the average size of all CTC clusters (c) and among homotypic (regression coefficient −0.20, 95% CI −0.76 to 0.35) or heterotypic (regression coefficient −0.31, 95% CI −1.21 to 0.59) clusters, separately (d). LME coefficients are also shown for control nonrandomized patients, not receiving digoxin therapy (regression coefficient 0.48, 95% CI −0.10 to 1.07 for homotypic clusters; regression coefficient −0.06, 95% CI −0.70 to 0.58 for heterotypic clusters). The cross bar in d represents the LME fixed-effect coefficient. e, The average cluster size at baseline and posttreatment (day 3 or day 7) paired by patient (n = 9). The boxes represent the lower quantile, median and upper quantile. The vertical lines show the range of values, and the gray lines connect paired values. P values were calculated using the one-sided paired t-test. f, The fold change of the average CTC cluster size post- over pretreatment in treated patients. In control patients, the fold change of the average CTC cluster size at day 3 or day 7 (according to smaller cluster size) over baseline is shown. Each point represents an individual patient, and the cross bar represents the median. P values were calculated using the one-sided Wilcoxon rank-sum test. g, Negative association between digoxin levels and normalized size of CTC clusters at day 7 (linear regression P = 0.14, β = −4.65). The points represent individual patients, the line represents the linear regression model and the shaded area represents the 95% CI of the fitted line. CTCAE, Common Terminology Criteria for Adverse Events; BM, bone marrow; ECG, electrocardiogram; SAE, serious adverse event. Panel a was created with BioRender.com.
What then has to happen is for something to then kill the cancer cells. Digoxin can't do that.
However, digoxin alone does not eliminate the existing tumour. The agent would have to be administered in combination with other substances that kill existing cancer cells.
Next, researchers want to develop new molecules based on digoxin that improve its ability to dissolve CTC clusters. The authors would also like to expand the work to other types of cancer that spread, such as prostate, colorectal or pancreatic cancer, and melanoma. Initial experiments in his laboratory have already begun.
Reference: Kurzeder C, Nguyen-Sträuli BD, Krol I, Ring A, et al. Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept study. Nature Medicine, 2025. DOI: 10.1038/s41591-024-03486-6
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