NFKB1 and melanoma: The genetic variants positively selected by MAPKi were not highly recurrent and could not fully explain clinical relapse.49 Instead, gene signature-based transcriptomic alterations in acquired MAPKi-resistant melanoma were highly recurrent, encompassing not only cell autonomous pathways (c-MET, LEF1, YAP1) but also patterns of CD8+ T-cell exhaustion such as down-regulation of antigen presentation machinery, dominance of M2 macrophages and NF-kB activation in the TME.48,49