Precision Therapy for RET-altered Cancers with RET Inhibitors

Overview

Journal Trends Cancer

Publisher Cell Press

Specialty Oncology

Date 2021 Aug 15

PMID 34391699

Citations 65

Authors

Kyaw Z Thein

Vamsidhar Velcheti

Blaine H M Mooers

Jie Wu

Vivek Subbiah

Affiliations

Soon will be listed here.

Abstract

Rearranged during transfection (RET) is involved in the physiological development of some organ systems. Activating RET alterations via either gene fusions or point mutations are potent oncogenic drivers in non-small cell lung cancer, thyroid cancer, and in multiple diverse cancers. RET-altered cancers were initially treated with multikinase inhibitors (MKIs). The efficacy of MKIs was modest at the expense of notable toxicities from their off-target activity. Recently, highly potent and RET-specific inhibitors selpercatinib and pralsetinib were successfully translated to the clinic and FDA approved. We summarize the current state-of-the-art therapeutics with preclinical and clinical insights of these novel RET inhibitors, acquired resistance mechanisms, and future outlooks.

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