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. Author manuscript; available in PMC: 2023 Apr 3.
Published in final edited form as: Clin Cancer Res. 2022 Oct 3;28(19):4278–4291. doi: 10.1158/1078-0432.CCR-22-0527

Figure 6. Targeting OLIG2 prevents recurrence of OLIG2−high MYC-amplified MB in vivo.

Figure 6.

(A) Analysis of OLIG2-CRISPR mediated knock down of OLIG2 protein in MB002 tumor by western blot. Control, ctrl.

(B) Mice survival curves for animals bearing MB002 tumors with overexpression of OLIG2-CRISPR1. Survival analysis was performed using Kaplan Meier. The p value is for the OLIG2-CRISPR+CSI compared to control-CRISPR+CSI.

(C) IHC staining for OLIG2 (green) in the relapsed tumors with overexpression of control (ctrl CRISPR) and OLIG2-CRISPR1. Tumor cells are indicated in red (mCherry)

(D-F) CT-179, an OLIG2-small molecule inhibitor, restricts MB002 subcutaneous tumor growth. Animals were euthanized when their body weight decreased by ~20% from initial weight. (D) Tumor volume was measured using calipers every 2 days during the course of the treatment. Data are shown as mean ± SD for tumor volume. p values were determined using one-way ANOVA followed by Tukey post-hoc test. Tumor volumes on day 12 of treatment were used in statistical analysis. (E) Tumor images at the time of sacrifice. (F) Western blot analysis showing that OLIG2 expression in flank tumors was reduced by CT-179 treatment.

(G) Schematic showing CT-179 treatment twice weekly for intracranial tumors. IT, intrathecal injection

(H-J) Animals bearing MB002 tumors treated with vehicle, CT-179, CSI alone or CSI + CT-179 by intrathecal injection. (H) Bioluminescence images of representative mice (X denotes animals euthanized before they could be imaged). (I) Kaplan Meier survival curves. p values were determined by Log-rank (Mantel-Cox) test. (J) Images of brains from representative animals. Red is mCherry, indicating tumor cells. Tissues were counterstained with DAPI. Animals were euthanized when their body weight decreased by ~20% from initial weight. The p value is for the CST+ CT-179 compared to CSI.

(K-L) Kaplan Meier survival curves for animals bearing Med-211FH (K) or RCMB20 (L) tumors treated with vehicle, CT-179, CSI alone or CSI + CT-179 by intrathecal injection. The p value is for the CST+ CT-179 compared to CSI.

(See also Figures S6 and S7).