Selective RET kinase inhibition for patients with RET-altered cancers.

ABSTRACT:

Background

Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed to inhibit diverse RET fusions, activating mutations and acquired resistance mutations.

Patients and methods

Potent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models. Due to clinical urgency, two patients with RET-altered, MKI-resistant cancers were treated with LOXO-292, utilizing rapid dose-titration gu

SUBMITTER: Subbiah V 

PROVIDER: S-EPMC6096733 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature