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. 2022 Dec 6;13(2):298–311. doi: 10.1158/2159-8290.CD-22-1066

Figure 4.

Figure 4. KRASG12D inhibition promotes tumor regressions in the autochthonous KPC/Y model. A, Tumor volumes (mm3) of KPC/Y tumors treated with vehicle control, MRTX1133, or MRTX1133 +αCD4/CD8. Growth curves show changes in tumor volume over 14 days of MRTX1133 treatment. n = 13–14/group. Each symbol represents the average tumor volume. Error bars, SEM. Statistics were determined using a two-way ANOVA with the Sidak multiple comparisons test with significance indicated (****, P < 0.0001). B, Waterfall plot of KPC/Y tumors in A treated with vehicle, MRTX1133, or MRTX1133 +αCD4/CD8 showing changes in tumor volume after 14 days of treatment. Each bar represents a single tumor. n = 13–14/group. C, Tumor volumes (mm3) of MRTX1133 and MRTX1133 +αCD4/CD8-treated KPC/Y tumors. Growth curves show changes in tumor volume over 14 days of MRTX1133 treatment and an additional 3 weeks of αCD4/CD8 in the T-cell depletion cohort. n = 6–8/group. Each symbol represents average tumor volume. Error bars, SEM. Statistics were determined using a two-way ANOVA with the Sidak multiple comparisons test with significance indicated (**, P < 0.01). D, Tumor volumes (mm3) of KPC/Y tumors (n = 7) treated with MRTX1133. Growth curves show changes in tumor volume over 14 days of MRTX1133 treatment and an additional 6 weeks off therapy. One mouse (10527) resumed MRTX1133 treatment at 63 days after enrollment and continued treatment for an additional 7 weeks. Each line represents a single tumor. E, Representative coimmunofluorescence images of p-ERK1/2, CK19, and DAPI in vehicle- and MRTX1133-treated KPC/Y tumors. Scale bars, 100 μm. Objective, 20×. F, Quantitation of p-ERK1/2 staining as percent area per HPF in control (n = 4) and MRTX1133-treated (n = 3) KPC/Y tumors. At least 3 fields of view were averaged per tumor. P values were determined by an unpaired Student t test. Error bars, indicate SD. G, Representative coimmunofluorescence images of αSMA, F4/80, and GFP in control- and MRTX1133-treated KPC/Y tumors. Scale bars, 100 μm. Objective, 20×. H, Quantitation of macrophages (F4/80+) and fibroblasts (αSMA+) as percent area per HPF in control- (n = 4) and MRTX1133-treated (n = 3) KPC/Y tumors. At least 3 fields of view were averaged per tumor. P values were determined using a two-way ANOVA with the Sidak multiple comparisons test. Error bars, SD.

KRASG12D inhibition promotes tumor regressions in the autochthonous KPC/Y model. A, Tumor volumes (mm3) of KPC/Y tumors treated with vehicle control, MRTX1133, or MRTX1133 + αCD4/CD8. Growth curves show changes in tumor volume over 14 days of MRTX1133 treatment. n = 13–14/group. Each symbol represents the average tumor volume. Error bars, SEM. Statistics were determined using a two-way ANOVA with the Sidak multiple comparisons test with significance indicated (****, P < 0.0001). B, Waterfall plot of KPC/Y tumors in A treated with vehicle, MRTX1133, or MRTX1133 + αCD4/CD8 showing changes in tumor volume after 14 days of treatment. Each bar represents a single tumor. n = 13–14/group. C, Tumor volumes (mm3) of MRTX1133 and MRTX1133 + αCD4/CD8-treated KPC/Y tumors. Growth curves show changes in tumor volume over 14 days of MRTX1133 treatment and an additional 3 weeks of αCD4/CD8 in the T-cell depletion cohort. n = 6–8/group. Each symbol represents average tumor volume. Error bars, SEM. Statistics were determined using a two-way ANOVA with the Sidak multiple comparisons test with significance indicated (**, P < 0.01). D, Tumor volumes (mm3) of KPC/Y tumors (n = 7) treated with MRTX1133. Growth curves show changes in tumor volume over 14 days of MRTX1133 treatment and an additional 6 weeks off therapy. One mouse (10527) resumed MRTX1133 treatment at 63 days after enrollment and continued treatment for an additional 7 weeks. Each line represents a single tumor. E, Representative coimmunofluorescence images of p-ERK1/2, CK19, and DAPI in vehicle- and MRTX1133-treated KPC/Y tumors. Scale bars, 100 μm. Objective, 20×. F, Quantitation of p-ERK1/2 staining as percent area per high-power field (HPF) in control-treated (n = 4) and MRTX1133-treated (n = 3) KPC/Y tumors. At least 3 fields of view were averaged per tumor. P values were determined by an unpaired Student t test. Error bars, SD. G, Representative coimmunofluorescence images of αSMA, F4/80, and GFP in control- and MRTX1133-treated KPC/Y tumors. Scale bars, 100 μm. Objective, 20×. H, Quantitation of macrophages (F4/80+) and fibroblasts (αSMA+) as percent area per HPF in control-treated (n = 4) and MRTX1133-treated (n = 3) KPC/Y tumors. At least 3 fields of view were averaged per tumor. P values were determined using a two-way ANOVA with the Sidak multiple comparisons test. Error bars, SD.