Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The presence of circulating tumor cell CTC clusters is associated with disease progression and reduced survival in a variety of cancer types.
An analysis of nine patients treated daily with a maintenance digoxin dose 0. Mechanistically, transcriptome profiling of CTCs highlighted downregulation of cellโcell adhesion and cell-cycle-related genes upon treatment with digoxin, in line with its cluster-dissolution activity. No treatment-related adverse events occurred. Breast cancer is the most diagnosed cancer among women globally 1.
In the past decade, multimodal approaches and innovative therapies have transformed the outlook of this lethal disease, leading to gains in patient survival 2. Despite these advances, nearly , women die of breast cancer each year worldwide 1 , largely due to the development of incurable distant metastases to vital organs 3. In this context, a potentially critical factor may lie within the underlying principles of most anticancer drugs.
Standard-of-care treatments are typically developed on the basis of their cytotoxic activity and are not necessarily designed to interfere with metastasis-relevant mechanisms 4 , 5. Consequently, there is an intriguing yet uncharted opportunity for the development of metastasis-targeted agents that disrupt the causes of metastasis themselves 4 , 5.
Circulating tumor cells CTCs are living cells that are shed from both primary and metastatic lesions into the bloodstream, acting as metastatic pioneers 6. The presence of CTCs has been firmly established to be predictive of poor prognosis in patients with breast cancer 7. Recent studies by us and others demonstrated that clusters of CTCs, defined as multicellular aggregates of cancer cells alone homotypic or in liaison with immune cells heterotypic , have a substantially higher metastatic capacity and a stronger association with a poor prognosis than single CTCs 8 , 9 , Preclinical studies further revealed unique biological properties and vulnerabilities of these clusters, such as stem-like and proliferation features dependent upon cellโcell adhesion integrity 8 , The primary objective of the study was to assess the effect of digoxin on CTC cluster size in patients with metastatic breast cancer.
