Skip to main content
. 2022 Sep 16;82(22):4261–4273. doi: 10.1158/0008-5472.CAN-21-3214

Figure 7.

Figure 7. Rbms3-silencing drives resistance to pathway-targeted inhibition of BRAFV600E while adapting sensitivity to inhibition of Porcupine. A, Representative images of H&E-stained lung sections harvested 11 weeks after initiation from BC mice following treatment with the indicated pharmacological agents starting at 6 weeks after initiation with 5×104 pfu lenti-CRE. BC mice were dosed once daily for 5 weeks with: (i) Vehicle control; (ii) dabrafenib (75 mg/kg) plus trametinib (1 mg/kg) or; (iii) LGK974 (5 mg/kg). B and C, Quantification of lung tumor burden in BC mice initiated with sgNT-CRE or sgRbms3-CRE and dosed with the indicated pharmacological agents as indicated. Mean tumor burden is graphed, and error bars represent SEM. N = 5–7 mice per dosing arm. Statistical analysis was performed using a one-way ANOVA (****, P < 0.0001).

Rbms3-silencing drives resistance to pathway-targeted inhibition of BRAFV600E while adapting sensitivity to inhibition of Porcupine. A–F, Representative images of H&E-stained lung sections harvested 11 weeks after initiation from BC mice following treatment with the indicated pharmacological agents starting at 6 weeks after initiation with 5 × 104 pfu lenti-CRE. BC mice were dosed once daily for 5 weeks with: (i) vehicle control; (ii) dabrafenib (75 mg/kg) plus trametinib (1 mg/kg); or (iii) LGK974 (5 mg/kg). G and H, Quantification of lung tumor burden in BC mice initiated with sgNT-CRE or sgRbms3-CRE and dosed with the indicated pharmacological agents as indicated. Mean tumor burden is graphed. I–N, Immunohistochemical analysis of pERK1/2 in BC mice following treatment with the indicated pharmacological agents. Error bars, SEM. N = 5–7 mice per dosing arm. Statistical analysis was performed using a one-way ANOVA; ****, P < 0.0001.