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

Prevalence of secondary RET mutations after SRIs was low, underscoring greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide development of novel therapeutic strategies.