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. Author manuscript; available in PMC: 2018 Jan 17.
Published in final edited form as: Nat Med. 2017 Jul 17;23(8):929–937. doi: 10.1038/nm.4369

Figure 5. Identification of a treatment to suppress the evolution of BRAF amplified clones.

Figure 5

(a) Immunoblot analysis (n = 2 independent experiments) of dox-induced A375 cells treated as shown (doses as in Fig. 4b) for 24h to determine the effect on ERK signaling intermediates. (b) As in a, but cells were treated for 72h to determine the effect on viability (n = 3, mean ± s.e.m). (c, d) Mice bearing PDX1D (c) or PDX1E (d) were treated with dabrafenib (RAFi), trametinib and/or SCH984 daily for 14 days followed by discontinuation of treatment to determine the effect on tumor growth (n = 5 mice, mean ± s.e.m). A vemurafenib analogue (PLX4720), alone or in combination, had a similar effect to dabrafenib (see below). Mice treated with the MEK/ERKi combination experienced significant toxicity leading to discontinuation of the experiment in (d). (e) Tumors that regrew after discontinuation of drug treatment from (c) were analyzed to determine BRAF CN by sequencing and BRAF protein expression by immunoblot analysis.