Journal: Cancer Discovery
Article Title: Epigenetic and Transcriptional Programs Define Osteosarcoma Subtypes and Establish Targetable Vulnerabilities
doi: 10.1158/2159-8290.CD-25-0237
Figure Lengend Snippet: EOD and LOD osteosarcomas have differential drug response. A, IC 50 curves showing the response to trametinib in vitro ( n = 16). The cell lines are colored based on the subtype (EOD/LOD). Drug response was measured after 7 days of treatment. Cell lines are listed in the order they appear, highest to lowest, at the highest concentration. B, Differential drug response to trametinib ( n = 15). Mean with SD with a Mann–Whitney test P value (**, 0.0022). C, IC 50 curves showing the response to AZD1152 in vitro ( n = 16). The cell lines are colored based on the c-MYC protein levels (c-MYC high/c-MYC low). D, Relationship between the c-MYC protein level and the IC 50 of the response to AURKBi (AZD1152). E, Cell injection and treatment schedule of EOD/LOD tumors. F, EOD tumors respond to AURKBi (AZD1152) in vivo in a subcutaneous model. Eight vehicle tumors, nine AZD1152-treated tumors, and nine trametinib-treated tumors. Tumor volume (mm 3 ) measured over time (left). Waterfall plot showing the decrease in tumor volume (center). Analysis of end point (right). Mean with SD with a Mann–Whitney test P value (***, 0.0001. G, LOD tumors respond to trametinib. Ten vehicle tumors, 12 AZD1152-treated tumors, and 12 trametinib-treated tumors. Tumor volume (mm 3 ) measured over time (left). Waterfall plot showing the change in tumor volume (center). Analysis of end point (right). Mean with SD with Wilcoxon test P values = (**, 0.0025; *, 0.0184). H, Strategy to evaluate drug combination in the PDXs. I, PDX (PDX833) shows a better response to combination therapy targeting both epigenetic cell states (AZD1152 and trametinib). Eight vehicle tumors, nine AZD1152-treated tumors, eight trametinib-treated tumors, and eight tumors treated with AZD1152 and trametinib. Tumor volume (mm 3 ) measured over time (left). Waterfall plot showing change in tumor volume (center). End point analysis comparing combination therapy with monotherapy (right). Mean with SD with Mann–Whitney test P values (***, 0.0007 & 0.0002; *, 0.0206). J, PDX (PDX774) shows a better response to combination therapy over time. Mean with SD with Mann–Whitney test P values (**, 0.0047). K, PDX (PDX526) also shows a better response to combination therapy over time. Mean with SD with Mann–Whitney test P values (**, 0.0043). L, PDX (PDX107) also shows a better response to combination therapy over time. Mean with SD with Mann–Whitney test P values (*, 0.0182). See also Supplementary Fig. S8.
Article Snippet: Barasertib-HQPA (AZD2811 or AZD1152, #HY-10126) and trametinib (#HY-10999) were purchased from MedChemExpress.
Techniques: In Vitro, Concentration Assay, MANN-WHITNEY, Injection, In Vivo
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