An updated patent review of rearranged during transfection (RET) kinase inhibitors (2016–present). (3rd October 2022)

• Record Type: Journal Article
• Authors: Acharya, Baku; Frett, Brendan
• Is Part Of: Expert opinion on therapeutic patents. Volume 32:Number 10(2022)
• Page Start: 1067
• Page End: 1077
• Publication Date: 2022-10-03
• Subjects: RET -- RET/PTC -- non-small cell lung cancer -- thyroid cancer -- precision medicine -- selpercatinib -- pralsetinib -- oncogene -- kinase inhibitor; Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1080/13543776.2022.2132851
• Languages: English
• ISSNs: 1354-3776

Abstract

ABSTRACT: Introduction: Rearranged during transfection (RET) is a transmembrane receptor tyrosine kinase. Aberrations in RET signaling due to mutations, gene fusions, or overexpression can lead to carcinomas. Six inhibitors have been approved for the treatment of RET-driven cancers: vandetanib, cabozantinib, lenvatinib, sorafenib, selpercatinib, and pralsetinib. Only selpercatinib and pralsetinib have been developed specifically for RET, while the remaining are multikinase inhibitors. Several other RET targeted candidates are under clinical development. Areas covered: This review covers recent patent literature describing small molecules that are active against RET since 2016 till present. Expert opinion: RET represents a major therapeutic target as its alterations occur in nearly 2% of all cancers. Recent approvals for RET targeted therapy have been developed specifically to target the RET oncogene. These approvals represent a paradigm shift from the last decade to now focus on the development of selective RET inhibitors rather than multikinase inhibitors. These newly approved RET inhibitors still have clinical issues with drug resistance. It is imperative that the next iteration of RET inhibitors are developed to block common treatment-resistant mutations. To accomplish this, RET inhibitors should be developed in concert with genomic profiling to ensure the most relevant clinical mutations are targeted.