Fig. 4
Second-line MAPK inhibition intervention reverts vemurafenib-progressed cell state and increases survival. a Matched melanoma differentiation marker gene expression from initial biopsy (IB), vemurafenib-progressed (VPr), and day 7 post second-line crossover cobimetinib-treated (7d PD) tumors plotted as a percent of IB. b Maximum percent tumor volume change from VPr by treatment. c Perforin transcript plotted as a percent of VPr plotted for three different day 7 post second-line crossover treated (P (gray, n = 3), Co (orange, n = 4), and CP (purple, n = 4)) tumors. d Fourth-order smoothed tumor volume plot for second-line treatments (see Extended Data Figure 7a for raw data). e Kaplan–Meier plot of animals by treatment group with median survival. Notably, no animals were killed in the combination treatment group due to tumor regrowth. This was not the case for the single agent α-PD-L1 (100% of animals) and cobimetinib (50% of animals) groups. *p < 0.05, **p < 0.005, ***p < 0.0005, ****p < 0.00005 by t-test in a. P-values in e by log-rank (Mantel–Cox) test. 7d PD: vemurafenib-progressed samples that are treated for 7 days with various second-line treatments; Co: vemurafenib-progressed cobimetinib-treated samples; CP: vemurafenib-progressed cobimetinib- and α-PD-L1-treated samples; IB: initial biopsy; P: vemurafenib-progressed α-PD-L1-treated samples; VPr: vemurafenib-progressed samples
