BRAF/MEK inhibition, oncogenic driver and tyrosine kinase inhibition, inhibition of angiogenesis, epigenetic modulation, and immunomodulation represent only a portion of the possible SM/ICI combinations being evaluated in cancer treatment, yet illustrate the mechanistic rationale for novel drug combinations utilized to combat metastatic melanoma (Figure 2). The gene discussed is BRAF; the disease is metastatic melanoma.