Precision oncology with selective RET inhibitor selpercatinib in -rearranged cancers.

Rearranged during transfection () is a protooncogene that encodes for receptor tyrosine kinase with downstream effects on multiple cellular pathways. Activating can occur and lead to uncontrolled cellular proliferation as a hallmark of cancer development. Oncogenic fusions are present in nearly 2% of patients with non-small cell lung cancer (NSCLC), 10-20% of patients with thyroid cancer, and <1% across the pan-cancer spectrum. In addition, mutations are drivers in 60% of sporadic medullary thyroid cancers and 99% of hereditary thyroid cancers. The discovery, rapid clinical translation, and trials leading to FDA approvals of selective inhibitors, selpercatinib and pralsetinib, have revolutionized the field of precision therapy. In this article, we review the current status on the use of the selective inhibitor, selpercatinib, in fusion-positive tumors: NSCLC, thyroid cancers, and the more recent tissue-agnostic activity leading to FDA approval.