Selpercatinib in the treatment of medullary and radioiodine-refractory differentiated thyroid cancer with RET mutation (literature review)

Selpercatinib is a novel, highly selective, small-molecule inhibitor of RET kinase that competes with adenosine triphosphate. In experimental models, this drug has demonstrated nanomolar activity against various RET gene alterations, including an acquired resistance mutation in the gatekeeper gene at residue V804, as well as antitumor activity in the brain. Selpercatinib inhibits wild-type and various mutated forms of RET, as well as vascular endothelial growth factor receptors (VEGFR1 and VEGFR3) with half-maximal inhibitory concentrations from 0.92 to 67.8 nM, and fibroblast growth factor receptors (FGFR1, FGFR2, and FGFR3).The article presents results of clinical studies on the efficacy and safety of selpercatinib in patients with radioiodine refractory differentiated thyroid cancer with alterations in RET gene and in patients with medullary thyroid cancer with a germinal or somatic mutation in this gene.