A novel RET transcription inhibitor called datelliptium seems to prevent the invasive and metastatic behavior of medullary thyroid carcinoma (MTC). It does so by reducing the epithelial-to-mesenchymal transition, migratory ability, and self-renewal capacity of MTC cells. This is according to a new study published in the journal Cancers.

This finding identifies datelliptium as a potential new therapeutic for the treatment of MTC that could replace or complement therapies currently used to treat MTC and increase patients’ lifespan and quality of life.

MTC is a type of aggressive thyroid cancer; it originates in the parafollicular C cells of the thyroid gland and tends to spread to other parts of the body, including the lymph nodes, liver, bones, and lungs. Although some cases of MTC occur sporadically, in around 20% to 25% of cases, the disease is familial and is linked to mutations in the RET (rearranged during transfection) proto-oncogene, which encodes for a receptor tyrosine kinase. One treatment approach for metastatic MTC, therefore, is tyrosine kinase inhibition. However, this approach has only been moderately successful.


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In the present study, a team of researchers led by Daekyu Sun, PhD., associate professor of pharmacology and toxicology at the University of Arizona, Tucson, evaluated the anti-invasive and antimetastatic potential of datelliptium in MTC.

It was already known that datelliptium stabilizes the RET G-quadruplex structures and suppresses RET transcription. Here, the researchers showed that datelliptium also suppressed epithelial-to-mesenchymal transition and significantly decreased the migration of MTC cells in a dose-dependent manner. Moreover, the study showed that datelliptium can significantly reduce the size of tumor spheroids from MTC cells and inhibit MTC tumor growth while having minimal systemic toxicity.

“Combining existing [tyrosine kinase inhibitors] with datelliptium, which offers a different mechanism of action, may enhance antitumor effects beyond the use of [tyrosine kinase inhibitors] alone.” the researchers wrote. They added that the effect of datelliptium in combination with selpercatinib or pralsetinib should be tested to determine whether such combinations may have better antitumor effects.

Reference

Alqahtani T, Alswied A, Sun D. Selective antitumor activity of datelliptium toward medullary thyroid carcinoma by downregulating RET transcriptional activity. Cancers (Basel). 2021;13(13):3288. doi:10.3390/cancers13133288