RET

Description

RET mutations and the RET fusion RET-PTC lead to activation of this tyrosine kinase receptor and are associated with thyroid cancers. RET point mutations are the most common mutations identified in medullary thyroid cancer (MTC) with germline and somatic mutations in RET associated with hereditary and sporadic forms, respectively. The most common somatic form mutation is M918T (exon 16) and a variety of other mutations effecting exons 10, 11 and 15 have been described. The prognostic significance of these mutations have been hotly debated in the field, however, data suggests that some RET mutation may confer drug resistance. Highly selective and well-tolerated RET inhibitors, selpercatinib (LOXO-292) and pralsetinib (BLU-667), have been FDA approved recently for the treatment of RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer.