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Can Digoxin Improve RAI Sensitivity in Resistant Nonmedullary Thyroid Cancer?

By: Susan Reckling
Posted: Monday, February 22, 2021

Although patients with nonmedullary thyroid cancer are often treated with radioactive iodide (RAI), some experience tumor dedifferentiation, with subsequent resistance to such therapy. In the continued search for an effective treatment for these patients, Theo S. Plantinga, PhD, of Radboud University Medical Center and Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands, and colleagues turned to digoxin, a medication used to treat various cardiac conditions, primarily atrial fibrillation. Based on their early research findings, “digoxin may represent a repositioned adjunctive treatment modality that suppresses tumor growth and improves RAI sensitivity in patients with RAI-refractory nonmedullary thyroid cancer.”

“Interestingly, digoxin-treated nonmedullary thyroid cancer patients were more prone to reach remission after RAI treatment, suggesting that digoxin treatment could be associated with a more favorable clinical outcome,” stated the investigators. However, these findings require validation in prospective human studies.

To better understand the in vivo effects of this cardiac medication in both mice and digoxin-treated patients with nonmedullary thyroid cancer, the researchers used three-dimensional ultrasonography for monitoring tumor growth in the mice. They also conducted post-mortem tissue studies consisting of both gene-expression profiling and measurement of intratumor autophagy activity. In addition, archived tumor material from 11 patients with nonanaplastic, nonmedullary thyroid cancer who received digoxin was compared with 11 matched control patients with this type of thyroid cancer who had not received digoxin.

After a short course of digoxin treatment, the investigators reported that tumor growth was inhibited in the mice, and iodine-124 accumulation was increased. “Digoxin-treated nonmedullary thyroid cancer patients exhibited significantly higher autophagy activity and a higher differentiation status as compared to matched control nonmedullary thyroid cancer patients, and were associated with favorable clinical outcome,” the authors commented. 

Disclosure: The study authors reported no conflicts of interest.

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