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In thyroid cancer clinical trials, agents targeting VEGF receptors (VEGFR) and RET, among other kinases, have led to partial responses but few complete or durable responses. The RAF-MEK-ERK and PI3K-AKT-mTOR signaling pathways are frequently activated in differentiated and medullary thyroid cancer (DTC and MTC) and may provide therapeutic targets for these diseases. We tested a novel drug combination targeting RAF, phosphoinositide 3-kinase (PI3K), and mTOR, plus VEGFR2 and RET, in thyroid cancer preclinical models with defined genetic backgrounds.

Synergistic Action of a RAF Inhibitor and a Dual PI3K/mTOR Inhibitor in Thyroid Cancer