biostudies-literatureUnknownWaliany SNCI NIH HHS<h4>Purpose</h4>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.<h4>Experimental design</h4>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.<h4>Results</h4Clinical cancer research : an official journal of the American Association for Cancer Researchhttps://www.ebi.ac.uk/biostudies/studies/S-EPMC12912800biostudies-literatureLandscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium.PMC12912800P30 CA008748R01 CA251591P50 CA265826R01 CA273224R01 CA164273R01 CA226864Smith KERSolomon BJPatel SAWeiler DSun LYeap BYMansfield ASNagasaka MLee DHFalcon CPatil TGainor JFRotow JKFruh MGadgeel SWirth LJLin JJLiu SVTan DSWDo AWeber UMCooper AJRiess JWUy NFGautschi OWaliany SFeng JPall GBaik CSDrilon ACheung KSYLai GGYLoong HHFPatel JDPennell NALeighl NBOu SIKim TMfalseLandscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium.<h4>Purpose</h4>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.<h4>Experimental design</h4>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.<h4>Results</h42026-01-01T00:00:00Z2026 Jan2026-07-16T00:32:47.819Z2026-07-09T13:09:57.242ZS-EPMC129128004153770410.1158/1078-0432.ccr-25-438210.1158/1078-0432.CCR-25-4382