Supplementary Materials and Methods, Supplementary Table 1, and Supplementary Figures 1 through 14 from An <i>In Vivo</i> Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma
journal contribution
posted on 2023-03-31, 00:24 authored by Jessica L.F. Teh, Timothy J. Purwin, Evan J. Greenawalt, Inna Chervoneva, Allison Goldberg, Michael A. Davies, Andrew E. Aplin<p>Supplementary Materials and Methods. Supplemental Table 1. Summary of melanoma cell lines grouped for mutations in CDKN2A, CDK4, BRAF and NRAS. Supplemental Figure 1. Low concentrations of palbociclib inhibited phosphorylation of RB1 and cyclin A2 expression in sensitive cell lines but not in less sensitive lines. Supplemental Figure 2. Mean plasma concentration for palbociclib. Mice were treated with control chow or palbociclib for 8 or 15 days. Supplemental Figure 3. Sensitivity of melanoma cells to trametinib. GI50 values were generated from dose-dependent curves from MTT cell viability assays. Supplemental Figure 4. Enhanced PARP cleavage in BRAF and NRAS mutant cells treated with trametinib or trametinib plus palbociclib. Supplemental Figure 5. Clustergram and scatter plot generated from apoptosis PCR Array. Supplemental Figure 6. Endogenous levels of survivin in a panel of melanoma cell lines. Supplemental Figure 7. Representative tumor size of 1205Lu xenografts measured by tdTomato fluorescence activity. Supplemental Figure 8. Average weight (g) of mice bearing 1205Lu xenografts treated in each cohort. Supplemental Figure 9. Average weight (g) of mice bearing WM1366 xenografts treated in each cohort. Supplemental Figure 10. Modulation of E2F activity in combination treated mice bearing WM1366 xenografts that did not show complete response. Supplemental Figure 11. E2F reactivation in WM1366 xenografts precedes resistance to MEK inhibitor or CDK4/6 inhibitor as measured by tdTomato activity. Supplemental Figure 12. Residual tdTomato signal in 1205Lu tumors of mice showing complete response by lack of palpable tumor. Supplemental Figure 13. Two heat maps of the most significantly up (A) and down (B) regulated pathways for CDK-R vs MEK-R, Combo-R vs MEK-R and Combo-R vs CDKR. Supplemental Figure 14. Validation of proteins from the RPPA analysis heatmap in Figure 6.</p>
