Fig. 3: OTX-2002 reduces tumor burden and MYC expression in HCC xenograft models. | Nature Communications

Fig. 3: OTX-2002 reduces tumor burden and MYC expression in HCC xenograft models.

From: Targeted transcriptional downregulation of MYC using epigenomic controllers demonstrates antitumor activity in hepatocellular carcinoma models

Fig. 3

A OTX-2002 in vivo efficacy as evaluated in Hep 3B subcutaneous xenografts in nude mice. Mice were administered treatment via intravenous injection (IV) once daily every five days (Q5D) or orally (PO) once daily (QD). Significance measured using two-way ANOVA comparing negative control (NC) mRNA to OTX-2002 treatments or PBS to sorafenib with adjusted p values for multiple comparisons; ****P < 0.0001. Results are from one independent experiment (n = 10 mice per group) and were repeated once. B Body weight changes over the course of the Hep 3B study in (A). C Survival curves for Hep 3B study in (A) with mice removed when they reached an arbitrary endpoint of >1000 mm3. Significance measured using Log-rank (Mantel-Cox) test comparing NC mRNA to OTX-2002 treatment (****P < 0.0001 or ***P = 0.0002) or PBS to sorafenib (***P = 0.0001). D Targeted methylation sequencing from extracted tumors at the end of study in (A) (n = 3 tumors per group). IHC Quantification for staining with MYC, Caspase-3, Ki67, and AFP (n = 10 mice per group except for sorafenib group where n = 9 mice). Significance measured using one-way ANOVA comparing NC mRNA to OTX-2002 or PBS to sorafenib with adjusted p-values for multiple comparisons; ****P < 0.0001. E OTX-2002 in vivo efficacy evaluated in orthotopic xenografts of luciferase-expressing Hep 3B cells in nude mice. Significance measured using two-way ANOVA comparing NC mRNA to OTX-2002 treatment or PBS to sorafenib with adjusted p-values for multiple comparisons; ****P < 0.0001. Results are from one independent experiment (n = 10 mice per group) and were repeated once. F Bodyweight change over course of the orthotopic study in (E). G Survival curves for Hep 3B orthotopic study in (E) with mice removed when they reached an arbitrary endpoint of FLux >109. Significance measured using Log-rank (Mantel-Cox) test comparing NC mRNA to OTX-2002 at 2 mg/kg Q5D (*P = 0.0064) or PBS to sorafenib (*P = 0.0397). For all relevant panels error bars represent mean ± standard error of the mean (SEM). Source data are provided as a Source Data file.

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