Figure 6. Tumor response to sotorasib treatment in K^G12CP mice.

(A) Waterfall plot representing the changes in tumor volumes of individual lung tumors present in Kras^+/FSFG12C;Trp53^F/F (K^G12CP) mice treated with sotorasib for 1 month (n = 15 mice/52 tumors). Tumors whose volume at the time of the first CT were smaller (orange) or larger (black bars) than 2 mm³ are indicated. (B) Tumor volumes determined by CT scans of representative tumors in K^G12CP mice treated with sotorasib for the indicated times. (C) CT scans (top) and 3D rendering (bottom) of lungs of K^G12CP mice at the beginning (day 0) and after sotorasib treatment for 4 and 20 weeks (w). Visible lesions are outlined by dotted lines (above) and in red (bottom). (D) Representative images of H&E, Ki67, pERK, cleaved caspase-3 (CC3), and CD8 staining in paraffin-embedded sections of tumors from K^G12CP mice either untreated (Control), treated with sotorasib for 1 or 2 weeks, and after they became resistant to sotorasib (Resistant). Scale bars: 20 μm. (E) Quantification of the percentages of Ki67⁺, CC3⁺, and CD8⁺ cells and pERK⁺ areas in sections of tumors from K^G12CP mice either untreated (C) or treated with sotorasib for 1 or 2 weeks, and after they became resistant to sotorasib (R). Data are represented as mean ± SEM. P values were calculated using 1-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001. (F) Percentages of the different histological grades (II to V) displayed by lung tumors in K^G12CP mice. Different shades of gray indicate increasing grades. Tumors present in K^G12CP mice untreated, treated with sotorasib for 1 or 2 weeks, and after they became resistant to sotorasib are indicated.