RAF1 and thyroid cancer: Described intrinsic (RAF/MEK/ERK pathway) and extrinsic (alternative pathways) mechanisms of acquired BRAF inhibitor resistance in thyroid cancer include: RAF/MEK/ERK pathway activation brought about through alternate BRAF splicing [11], activation of the PI3K/AKT pathway through c-MET [12], autocrine NRG1- mediated HER3 receptor activation of the PI3K/AKT and RAS/RAF/MEK/ERK pathways [13], and autocrine IL-6-mediated JAK/STAT3 and RAS/RAF/MEK/ERK pathway activation [14].