Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial.

Strikingly, pathway analysis showed highly significant downregulation of cell-cycle-related genes (G2/M transition and E2F targets, for example, CCNB2 , PLK1 , CHECK2 and CDC25 ; P < 0.05) and cell–cell adhesion molecules (for example, PCDH12 , CHD4 and CHD24 ; P < 0.05) compared with CTCs deriving from blood samples obtained before digoxin intake (Extended Data Fig. 5d , with the top 30 ontologies shown in Extended Data Fig. 6 ).

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Interestingly, despite the small treated cohort, a numerical trend toward a higher digoxin serum concentration and stronger reduction in the average cluster size at day 7 was observed (secondary endpoint) (linear regression coefficient −4.65, P = 0.14; Fig. 1g ), suggesting that higher digoxin serum levels or more potent Na + /K + ATPase inhibitors could be more effective in cluster dissolution.

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