For example, in melanoma, gain-of-function CRISPR screens have identified SMAD3, BIRC3, and SLC9A5 as main drivers of resistance to BRAF inhibitors, but only the upregulation of SMAD3 transcriptional activity induces a mesenchymal-like phenotype as well as BRAFi resistance [107]. This evidence concerns the gene SMAD3 and melanoma.