Fig. 6: G361 melanoma cells altered signaling signature and treatment.

a Barcode representing the PaSSS of G361 cells, namely the set of active unbalanced processes identified by PaSSS analysis. b Zoom-in images of the unbalanced processes active in G361 cells, and the drugs targeting the central proteins in each process. The upregulated proteins are colored red and the downregulated proteins are colored blue. c, d Survival rates of cells in response to different therapies. The cells were treated with the predicted combination (*) to target G361, the treatments used in the clinics for BRAF mutated melanoma malignancies, monotherapies of each treatment and the predicted combination used to target BRAF mutated melanoma cell line A375. The combination predicted to target G361 was more efficient than any other treatment. e Results of the survival assay (shown in panels c and d) are shown as a heatmap. f Western blot results after treatment with different therapies. The predicted combination depletes the signaling in G361 cells as represented by a decrease in phosphorylation levels of pS6, pERK, and pAkt. Akt remains active when the cells are treated with dabrafenib or dabrafenib + trametinib. g G361 cells were treated as indicated for 72 h and then the viability of the cells was measured in an MTT assay. The effect of the predicted combination (marked in with an asterisk sign) was superior to combinations and single drugs expected to partially inhibit the cell line-specific altered signaling signature.