Although targeted BRAF inhibition with vemurafenib or dabrafenib, or combined BRAF and MEK1/2 inhibitors (vemurafenib/trametinib, dabrafenib/cobimetinib, or encorafenib/binimetinib) are now mainstays metastatic melanoma treatment, therapeutic resistance poses a significant clinical challenge (9), and calls for new strategies targeting therapeutic resistance, melanoma recurrence, and metastatic progression (Fig. 1A). This evidence concerns the gene MAP2K1 and melanoma.