Vertical inhibition of BRAFV600E→MEK→ERK MAP kinase signaling with combinations of inhibitors of BRAFV600E (vemu-, dab-, or encorafenib) plus MEK1/2 (cobi-, tram-, or binimetinib) are FDA-approved first-line treatment strategies for patients with advanced BRAFV600-driven melanoma, non-small-cell lung carcinoma (NSCLC), or thyroid cancer. The gene discussed is MAP2K1; the disease is thyroid cancer.