Abstract
Medullary thyroid carcinoma (MTC) is a rare but aggressive thyroid tumor, with 25% of hereditary and 75% of sporadic forms. RET mutations are found in 98% of hereditary MTC and in 55% of sporadic MTC. The most frequent somatic RET mutation occurs in codon M918, reported in up to 90% of RET-positive MTC cases. Selpercatinib and pralsetinib, tyrosine-kinase inhibitors with a high specificity for RET protein, recently obtained FDA approval for the treatment of Lung and Thyroid Cancers with RET gene mutations or fusions. In MTC patients, phase I/II studies with RET inhibitors reported overall response rates of 73% and phase III are ongoing. Here we describe the case of a patient with metastatic MTC who harbored two somatic variants of unknown significance (VUS) in the RET gene and responded to Pralsetinib.
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