Numerous avenues that lead to acquired resistance to RAFis generally utilize multiple methods to target the same or parallel pathways.366 Vertical inhibition of the MAPK signaling pathway using combinations of RAFi together with MEK inhibitors has received FDA approval as a first-line treatment strategy for patients with advanced RAF-mutant melanoma, NSCLC, and thyroid cancer. The gene discussed is RAF1; the disease is thyroid gland carcinoma.