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. 2022 Jan 12;13(1):54. doi: 10.1038/s41419-022-04502-8

Fig. 8. FAK inhibition sensitizes resistant mutBRAF and mutNRAS melanoma to mutation-specific targeted kinase inhibition.

Fig. 8

A Parental mutBRAF Malme3M and WM3248 MM cells were conditioned to 1 µM BRAF inhibitor dabrafenib (Dabra); mutNRAS SkMel2 and SkMel147 cells to 1 nM MEK inhibitor trametinib (Trame). mutBRAF parental (p) and conditioned (c) cells were treated with 10 µM dabrafenib, dabrafenib + 1 µM trametinib, 2.5, 5, or 10 µM of the iFAK defactinib alone and in combination with 10 µM dabrafenib. Parental (p) and conditioned (c) mutNRAS cells were treated with 1 µM trametinib, trametinib + 10 µM dabrafenib, 2.5, 5 or 10 µM of the iFAK defactinib alone and in combination with trametinib. Cell death was monitored by PI (1 µg/ml) uptake using IncuCyte® live-cell analysis for 48 h. B Three mutBRAF (M45, M53, M59) and three mutNRAS (M10, M20, M32) cell samples freshly isolated from patients with relapsed melanoma metastases were treated as in A according to their mutation status. Cell death was monitored by PI (1 µg/ml) uptake using IncuCyte® technology for 48 h. C The same patient-derived metastatic cell samples as in (B) were treated with IZI50, 2.5, 5, or 10 µM of the iFAK defactinib alone and in combination with IZI50. Cell death was monitored by PI (1 µg/ml) uptake using IncuCyte® technology for 48 h. For each experiment n = 3 is shown (*p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; n.s. = not significant).