Fig. 6: DT2216 increases the antitumor efficacy of BQ in patient-derived PDAC organoids and PDAC mouse models.
From: De novo pyrimidine biosynthesis inhibition synergizes with BCL-XL targeting in pancreatic cancer
a–d Synergy score heatmaps based on cell viability data from patient-derived PDAC organoids treated with DT2216 and BQ. Synergy score calculated using the HSA model in SynergyFinder. Experiments were repeated two independent times, and data are shown as mean HSA score of three technical replicates from one experiment. e Experimental design of (f). f Tumor volume of PaTu-8902 BCL-XL KO tumors (non-targeting n = 7, non-targeting + BQ n = 7, BCL-XL KO n = 8, BCL-XL KO + BQ n = 9 per arm) after treatment with vehicle or 10 mg/kg BQ three times a week for 3 weeks. Error bars represent s.e.m. Statistical significance determined by ordinary one-way ANOVA test. *p  <  0.05, ***p  <  0.001, ****p  <  0.0001 (p = 0.024, non-targeting vs. BCL-XL KO; p = 0.020, non-targeting + BQ vs. BCL-XL KO + BQ; p = 0.0007, non-targeting vs. non-targeting + BQ; p = 0.0002, BCL-XL KO vs. BCL-XL KO + BQ). g Experimental design of PaTu-8902 and HPAC xenograft flank tumor studies. h, i Tumor growth curves from PaTu-8902 (h, n = 13 per arm) and HPAC (i, n = 7 per arm) xenograft mouse models treated with vehicle, BQ, DT2216, or combination for 3 weeks. Error bars represent s.e.m. Statistical significance determined by one-way ANOVA. h *p = 0.014, BQ vs BQ + DT2216; ****p  <  0.0001. i ***p < 0.001 (p = 0.0003, BQ vs BQ + DT2216; p  =  0.0004, DT2216 vs BQ + DT2216; p <  0.0001, Vehicle vs BQ + DT2216. j Experimental design of KPCY 6694 C2 syngeneic flank allograft study in (k). k Tumor growth curves of KPCY 6694 C2 syngeneic flank model treated with vehicle (n = 12), BQ (n = 13), DT2216 (n = 11) or combination (n = 11) for 3 weeks. For flank-based tumor in vivo studies, tumors were measured twice a week. Error bars represent s.e.m. Statistical significance determined by one-way ANOVA (**p = 0.0034: BQ vs. BQ + DT2216; ****p  <  0.0001: Vehicle or DT2216 vs. BQ + DT2216). l Experimental design of KPCY 6694 C2 syngeneic orthotopic tumor study. m Tumor weight of KPCY 6694 C2 orthotopic tumors (n = 10 per arm, n = 8 for BQ + DT2216 group) after treatment with vehicle, BQ, DT2216, or combination for 16 days. Error bars represent ± s.e.m. Statistical significance determined by one-way ANOVA test, *p  <  0.05, **p  <  0.01 (p = 0.025, BQ vs BQ + DT2216; p = 0.001, Vehicle vs. BQ + DT2216; p = 0.003, DT2216 vs. BQ + DT2216). (Mancias, J. (2025) https://BioRender.com/i4zww2l). Source data provided as Source Data file.
