RET is a receptor protein with tyrosine kinase activity that can transfer a phosphate group from ATP to other molecules modifying their shape and function in signaling pathways that are essential to organogenesis and tissue maintenance. Gain-of-function genetic alterations in RET, e.g. point mutations or chromosomal rearrangements that produce oncogenic fusions, are implicated in some types of cancer, especially those of thyroid, and less frequently, lung and breast cancers, among others. Current anticancer therapies agaisnt RET-driven tumors are based on ATP-competitive inhibitors of the RET catalytic activity. Second generation inhibitors, which include LOXO-292 (selpercatinib) and BLU-667 (pralsetinib), have been approved by the FDA and result in remarkable clinical responses in cancer patients.