Two major problems with TARs in BRAF-mutated melanoma are the occurrence of non-melanoma secondary skin cancer, and the development of resistance while on therapy.24 Studies showed BRAFi combined with MEKi could increase the medium PFS from 7-9 months with BRAFi monotherapy to 11-15 months.13,14,42 This might due to the MEKi can avoid reactivation of the MAPK pathway by BRAFi monotherapy, and thus reduce the skin toxicity. Here, BRAF is linked to skin cancer.