Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium.

ABSTRACT:

Purpose

Rearranged during transfection (RET) alterations are oncogenic drivers across solid tumors. Selective RET inhibitors (SRIs) selpercatinib and pralsetinib have transformed outcomes for patients with RET-altered malignancies. Limited knowledge exists on genomic mechanisms of resistance to SRIs.

Experimental design

We established 'RETgistry,' a global consortium of patients with advanced RET-altered solid tumors who received SRIs and underwent post-progression tissue or plasma biopsies assessed by next-generation sequencing. Frequencies of secondary RET resistance mutations and acquired non-RET gene alterations were determined. Progression-free survival (PFS) and time to treatment discontinuation (TTD) on first SRI were estimated with Kaplan-Meier method.

Results

SUBMITTER: Waliany S 

PROVIDER: S-EPMC12912800 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature