Supplementary Information from The IGF1R/INSR Inhibitor BI 885578 Selectively Inhibits Growth of IGF2-Overexpressing Colorectal Cancer Tumors and Potentiates the Efficacy of Anti-VEGF Therapy (2023)

&lt;p&gt;The following information of relevance to the manuscript is included: The source and authentication of all cell lines is included in Supplementary Table S1 and is of importance for validation of the results described in the manuscript. Data showing the mutual exclusivity and co-occurrence of IGF2 overexpression with other common molecular alterations found in CRC is included in Supplementary Tables S2 and S3, respectively. This information is of importance for understanding the different oncogenic pathways that are commonly present in IGF2-overexpressing CRC tumors. The sensitivity of cell lines to two structurally divergent IGF1R/INSR inhibitors is shown in Supplementary Table S4. This is of importance to validate that the BI 885578 sensitivity of the cell lines is related to IGF1R/INSR inhibition and not the inhibition of potential BI 885578 off-targets. The in vitro sensitivity data for non-CRC cell lines is shown in Supplementary Table S5 which corresponds to the data presented in Figure 6. This is of importance for the reader to have access to the GI50 data for each cell lines tested. The expression of IGF2 on a separate data set from TCGA is shown in Supplementary Figure S1 and is of importance to validate the frequency of IGF2 overexpressing colon tumors. The expression of total IGF1R and total Akt protein by CRC cell lines is shown in Supplementary Figure S2 and this is of importance as it demonstrates that the absence of phospho-IGF1R or phospho-Akt signals in some cell lines is not due to low expression of the corresponding total proteins. The effect of BI 885578 on phospho-IGF1R and phospho-Akt levels in vivo is shown in Supplementary Figure S3 to demonstrated that dosing of the compound led to engagement of the IGF pathway in vivo. The tumor growth kinetics are shown in Supplementary Figure S4 order to demonstrate the time-course of response of the different tumor models to BI 885578, anti-VEGF-A and the combination of these compounds. The change in mouse body weight data is shown in Supplementary Figure S5 to confirm that BI 885578, anti-VEGF and the combination of these compounds were tolerated. The efficacy of BI 885578 in combination with diverse agents used in CRC is shown in Supplementary Figure S6 and has relevance for identification of the most promising combinations that could potentially be applied in future clinical studies with BI 885578. The change in mouse body weight data is shown in Supplementary Figure S7 to confirm that the compounds used in this study were tolerated. The effect of BI 885578 on HIF1-alpha and VEGF-A expression is shown in Supplementary Figures S8 and S9, respectively. This has relevance for understanding the role of IGF2 in promoting the expression of these pro-angiogenic proteins. The expression of IGF1R protein by non-CRC cell lines is shown in Supplementary Figure S10 and this is of importance as it demonstrates that the absence of phospho-IGF1R signals in some cell lines is not due to low expression of total IGF1R.&lt;/p&gt;