This model made it possible to observe the effective inhibition of BRAFi on the proliferation of MM cells (wild-type or mutated BRAF V600E) in coculture within the 3D models: SK-MEL-2 cells were sensitive to BRAFi in the 3D coculture, while they were resistant in the 2D configuration, highlighting that paracrine signaling in coculture models and extracellular matrix components are key points for drug efficiency. Here, BRAF is linked to Miyoshi myopathy.