Fig. 5: Induced resistance against afatinib and crizotinib combination is reversible. PMEL and PI3K-p85 protein expression is upregulated in afatinib and crizotinib combination resistant cells. | Cell Death & Disease

Fig. 5: Induced resistance against afatinib and crizotinib combination is reversible. PMEL and PI3K-p85 protein expression is upregulated in afatinib and crizotinib combination resistant cells.

From: Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma

Fig. 5

a Schematic showing the ‘drug holiday’ model used in this study where A375 cells were induced with resistance towards IC50 values of afatinib, crizotinib or the combination. b 2D MTS assay showing cell viability in the resistant cell lines against single or combination treatment. Induced resistance could be reverted back after keeping cells off drugs for 10 days. The resistance developed to the combination treatment was more than that achieved towards either drug alone (error bars represent mean ± SD; n = 3; p < 0.01). c Heat map with supervised clustering showing changes in protein candidates of selected genes as analyzed by RPPA when comparing drug resistant A375 cell lines with sensitive A375 cells (n = 3 technical replicates). d mRNA expression of genes associated with afatinib and crizotinib combination resistance, PMEL and PI3K-p85, in two matched cases from CMM patients who received BRAFi, utilizing AmpliSEQ data. Samples were collected before start of therapy and at progression. e Table showing AmpliSEQ data from the same matched cases as in d for other candidates associated with afatinib and crizotinib combination resistance.

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