Supplementary Tables and Figures from Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance
Table S1. Summary of CC-90003 specificity data resulting from cellular and biochemical assays. Table S2. Response of BRAF mutant cell lines to CC-90003 ERK 1/2 inhibition. Table S3. Summary of dose finding efficacy study in HCT-116 xenograft model. Figure S1. CC-90003 Mass spectrometry analysis of CC-90003 covalent ERK1/2 binding. Figure S2. CC-90003 Inhibits proliferation and induces apoptosis in a panel of KRAS mutant Lung, Pancreatic and Colorectal cancer cell lines. Figure S3. Assessment of ERK inhibitor PD markers in BRAF and KRAS mutant Cancer Models. Figure S4. CC-90003 inhibits proliferation of a subset of BRAF and KRAS mutant cell lung cancer lines and induces cell death more robustly, compared to published inhibitors. Figure S5. CC-90003 inhibits colony formation in a set of KRAS mutant PDX models ex vivo. Figure S6. CC-90003 does not reduce body weights of animals bearing KRAS mutant PDX derived tumors. Figure S7. Genes differentially expressed in CXF-243 PDX model compared to other models used in the study. Figure S8. Genes differentially expressed in CXF-243, CXF-975 and CXF-1034 PDX models compared to other models used in the study. Figure S9. Combination of CC-90003 with EGFR inhibitor Afatinib and NK inhibitor JNK-IN-8. Figure S10. Quantification of Western Blot data in Figure 4. Figure S11. CC-90003 does not reduce body weights of animals bearing LXFA-1674 KRAS mutant lung cancer PDX derived tumors. Figure S12. Regrowth of LXFA-1674 KRAS mutant lung cancer PDX derived tumors following discontinuation of treatment by Docetaxel and CC-90003 combination with Docetaxel. Figure S13. CC-90003 alone and in combination with Docetaxel modulates stemness program in ex vivo serial passaging Mammocult assay.