To the best of our knowledge, this is the first study demonstrating i) the expression and involvement of a novel truncated ALK protein (ALKRES) in drug-resistance, ii) that the inhibition of ALK restores sensitivity to BRAF inhibitors; iii) the presence of functional ALKRES within EVs, which likely mediates the transfer of drug resistance and iv) that the combined inhibition of BRAF and ALK is a promising clinical treatment option for certain melanoma patients. Here, BRAF is linked to melanoma.