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AACR 2021: Can a Plant-Derived Alkaloid Reprogram the Inflammatory Environment in Thyroid Cancer?

By: Susan Reckling
Posted: Thursday, April 15, 2021

With a 5-year survival rate of less than 5%, anaplastic thyroid cancer is generally refractory to conventional therapies. Given its aggressive and inflammatory nature, Xiu-Min Li, MD, MS, of New York Medical College, Valhalla, and colleagues proposed that a holistic approach intended to reprogram the inflammatory tumor microenvironment of patients with this rare cancer might prove to be of benefit. With this in mind, they turned to berberine—a natural plant-derived alkaloid used in traditional Chinese medicine—given its antimicrobial and anti-inflammatory properties. The study findings, which were presented during the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract 317), suggested berberine may make anaplastic thyroid cancer more amenable to combination therapy with small-molecule inhibitors or other immunotherapies.

“The ability for berberine to alleviate the pro-inflammatory phenotype of anaplastic thyroid cancer and remodel its immune environment, while simultaneously depressing overactive signaling in these cell survival pathways, make mark it as an important agent…,” stated the investigators.

When Dr. Li and colleagues compared exosomes secreted from both anaplastic thyroid cancer and papillary thyroid cancer, they observed distinct miRNA expression. On comparative analysis, the following 10 miRNAs were specifically downregulated in the exosomes from the anaplastic thyroid cancer cells: hsa-miR-26b-5p, hsa-miR-125b-5p, hsamiR-138-5p, hsa-miR-148a-5p, hsamiR-152-5p, hsa-miR-191-5p, hsa-miR-9-5p, hsa-miR-21-5p, hsa-miR-134-5p, and hsa-miR-379-5p. According to the researchers, the first six miRNAs were found to be tumor suppressors; thus, their downregulation was thought to contribute to the metastatic nature of this type of thyroid cancer and perhaps its refractoriness to conventional therapies. In addition, berberine was found to significantly downregulate phosphorylation of MEK, ERK, and ribosomal protein S6 in proliferating anaplastic thyroid cancer cells, reportedly with a dose as low as 10 mM.

Disclosure: The study authors reported no conflicts of interest.

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