Using CD133 and BMI1 as biological markers of cancer malignancy58,59, we found that melanoma patient tissues with high grade expression of CD133 and BMI1 were associated with high levels of ITGB3, IGF1R, and JNK, as well as co-expression of LGR5 + HDGF (Figure 4D–4H), where these hits were selected from the pair-wise sgRNA screening library and calculated as efficient synergistic pairs for sensitizing BRAFi resistance. Here, HDGF is linked to melanoma.