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. 2021 Sep 8;6(17):e148392. doi: 10.1172/jci.insight.148392

Figure 7. Concomitant targeting of CDK4 and MAPK pathways augments response in Kras-mutant autochthonous lung tumors.

Figure 7

(A) IHC for indicated markers on KrasLSL/+, KrasLSL/+ Pflox/flox, and KrasLSL/+ M–/– lung sections 18–20 weeks after Ad-Cre infection. Scale bar: 50 μm. (B) Percentage change in overall lung tumor area of KrasLSL/+, KrasLSL/+ Pflox/flox, and KrasLSL/+ M–/– mice after 6–8 weeks of daily treatment with AZD6244 (25 mg/kg), palbociclib (50 mg/kg), or both as assessed by micro-CT imaging of mouse lungs. Significance was determined using Brown-Forsythe and Welch ANOVA tests. (C and D) IHC for indicated markers on lung sections from KrasLSL/+ Pflox/flox and KrasLSL/+ M–/– mice treated with AZD6244 and palbociclib for 6–8 weeks. Scale bar: 50 μm. Data are shown as mean. ***P < 0.005; **P < 0.001; *P < 0.05. (E) Proposed working model demonstrating differential CDK4 and MAPK signaling pathway activation and sensitivity to CDK4 and MEK inhibitor treatments between epithelial and mesenchymal lung cancer cells due to ZEB1 regulation of p21 expression.