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. 2022 Jun 16;21(8):1306–1317. doi: 10.1158/1535-7163.MCT-21-0598

Figure 2.

Figure 2. Combination therapy of ribociclib with gemcitabine improves survival of mice bearing G3MB tumors. A and B, Treatment schedules for human and mouse models, respectively. C—G, Mice bearing PDOX MB002 tumor cells treated with vehicle (black lines), ribociclib [100 mg/kg, continuous daily by oral gavage (OG), red lines], gemcitabine (60 mg/kg, i.v., day1 then every 2 weeks, blue lines), or the combination (purple lines) until moribund. H–K, Mice bearing mouse tumor #2416 treated with vehicle (black lines), ribociclib [100 or 200 mg/kg, day1–21 (3 weeks), OG, red lines], gemcitabine (60 mg/kg, i.v., day 1 then every 2 weeks, blue lines), or the combination of gemcitabine (60 mg/kg, i.v., day1 then every 2 weeks) with ribociclib (100 or 200 mg/kg, day1–21, OG, purple lines). Mice were treated with sequential cycles of therapy until moribund. C and H, Kaplan–Meier survival plots for all treatment groups. Comparison between treatment groups using log-rank test adjusted for multiple comparisons [not significant (n.s.), adjusted P ≤ 0.05 (*), adjusted P ≤ 0.005 (**), and adjusted P ≤ 0.0005 (***)]. Mice were censored if they died or required humane euthanasia not related to tumor and without preceding neurologic symptoms (e.g., death during sedation for imaging). Mice were imaged twice weekly by bioluminescence imaging (BLI). D and I, BLI pictures at different time points from enrollment through moribund stage represented for one mouse per treatment group. Mice were selected based on tumor and spinal growth median behavior. E, F, and J, BLI increase from enrollment (LOG10 transformation) for brain (E and J) and spine [F; Mann–Whitney test, P ≤ 0.05 (*), P ≤ 0.01 (**)]. For all BLI signal curves, see Supplementary Fig. S3. G and K, Endpoint BLI images of mice with visible spinal signal for MB002 (G), and #2416 (K), based on respective scales. Please note that the endpoint images of the vehicle and ribociclib mice presented in D were the same as in G where they are represented as part of all the mice imaged at endpoint in the study.

Combination therapy of ribociclib with gemcitabine improves survival of mice bearing G3MB tumors. A and B, Treatment schedules for human and mouse models, respectively. C–G, Mice bearing PDOX MB002 tumor cells treated with vehicle (black lines), ribociclib [100 mg/kg, continuous daily by oral gavage (OG), red lines], gemcitabine (60 mg/kg, i.v., day1 then every 2 weeks, blue lines), or the combination (purple lines) until moribund. H–K, Mice bearing mouse tumor #2416 treated with vehicle (black lines), ribociclib [100 or 200 mg/kg, day1–21 (3 weeks), OG, red lines], gemcitabine (60 mg/kg, i.v., day 1 then every 2 weeks, blue lines), or the combination of gemcitabine (60 mg/kg, i.v., day1 then every 2 weeks) with ribociclib (100 or 200 mg/kg, day1–21, OG, purple lines). Mice were treated with sequential cycles of therapy until moribund. C and H, Kaplan–Meier survival plots for all treatment groups. Comparison between treatment groups using log-rank test adjusted for multiple comparisons [not significant (n.s.), adjusted P ≤ 0.05 (*), adjusted P ≤ 0.005 (**), and adjusted P ≤ 0.0005 (***)]. Mice were censored if they died or required humane euthanasia not related to tumor and without preceding neurologic symptoms (e.g., death during sedation for imaging). Mice were imaged twice weekly by bioluminescence imaging (BLI). D and I, BLI pictures at different time points from enrollment through moribund stage represented for one mouse per treatment group. Mice were selected based on tumor and spinal growth median behavior. E, F, and J, BLI increase from enrollment (LOG10 transformation) for brain (E and J) and spine [F; Mann–Whitney test, P ≤ 0.05 (*), P ≤ 0.01 (**)]. For all BLI signal curves, see Supplementary Fig. S3. G and K, Endpoint BLI images of mice with visible spinal signal for MB002 (G), and #2416 (K), based on respective scales. Please note that the endpoint images of the vehicle and ribociclib mice presented in D were the same as in G where they are represented as part of all the mice imaged at endpoint in the study.