Fig. 8
Combination of BETi and CDK4/CDK6 attenuates resistance in flank models a Cumulative doubling of D458 cells passaged in DMSO, LEE011 (500 nM or 1 μM), JQ1 (1 μM) or the combination of JQ1 (1 μM) with LEE011 at either 500 nM or 1 μM. Data from three independent replicates are shown, error bars depict mean ± SEM. For all panels, asterisks denote statistically significant differences (*p < 0.05, **p < 0.01, ***p < 0.001) as determined by two-tailed unpaired t-tests. Source data: Source Data File. b Growth of D458 flank xenografts treated with vehicle, JQ1 (50 mg/kg/day), LEE011 (75 mg/kg/day) or the combination of both compounds (JQ1 50 mg/kg/day and LEE011 75 mg/kg/day). Three vehicle treated mice were euthanized on day 15 due to their tumor size (shown by arrow). Data represent mean tumor volume (n = 10), normalized to day 1, ± SEM. Large circles denote time points with significant (p < 0.0001) improvement in tumor volume relative to DMSO controls. Asterisk denotes significant (p < 0.05) improvement in tumor volume among mice treated with JQ1 and LEE011 relative to those treated with JQ1 alone as determined by two-tailed unpaired t-tests. Source data: Source Data File. c Growth of MB002 flank xenografts treated with vehicle, JQ1 (50 mg/kg/day), LEE011 (75 mg/kg/day or the combination of both compounds (JQ1 50 mg/kg/day and LEE011 75 mg/kg/day). Arrows depict days in which mice were euthanized due to their tumor size. Data represent mean tumor volume (n = 10), normalized to day 1, ± SEM. Medium and large circles denote significant (p < 0.05 and p < 0.0001, respectively) differences between treated tumors at each time point relative to DMSO controls. Asterisks denote statistically significant improvements in tumor volume among mice treated with JQ1 and LEE011 relative to those treated with JQ1 alone (*p < 0.05, **p < 0.01, ***p < 0.001) as determined by two-tailed unpaired t-tests. Source data: Source Data File. d Gene sets enriched in mRNA extracted from in vivo D458 flank xenografts treated with JQ1 relative to xenografts treated JQ1 and LEE011 (and thus suppressed by the combination of JQ1 and LEE011)
