Thyroid. 2021 Aug 18. doi: 10.1089/thy.2021.0144. Online ahead of print.
ABSTRACT
BACKGROUND: Metastatic thyroid cancers may dedifferentiate and become radioactive iodine refractory. The redifferentiating effect of pharmacological drugs was reported with inhibitors of the MAPK pathway in cancer with point mutation in oncogenes. The potential redifferentiating effect of inhibitors targeting oncogenic fusion genes is only suggested by a recent and unique publication using larotrectin ib in a NTRK rearranged tumor. Patients finding. Selpercatinib a highly selective RET inhibitor, was recently approved by the FDA for the treatment of RET fusion-positive lung and thyroid cancers. We had the unprecedented opportunity to observe restoration of iodine-131 uptake after selpercatinib treatment for a non-radioiodine avid metastatic thyroid cancer with a RET/PTC3 fusion gene.
CONCLUSION: This finding of a redifferentiation effect with selpercatinib targeting a RET fusion gene, reinforces the proof of concept of this new therapeutic opportunity. Therefore, future clinical trials and treatment strategies must not forget to evaluate the redifferentiating effect of drugs targeting gene rearrangements. Furthermore, the combined approach with a targeted therapy and radioactive iodine may increase anti-tumor efficacy and minimize acquired resistance to RET inhibitors.
PMID:34405703 | DOI:10.1089/thy.2021.0144
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