Fig. 7

NR5A2 inhibition targets CSCs in vivo and extends survival in preclinical PDAC models. A qPCR analysis for NR5A2, SOX2, MYC and CDKN1A mRNA levels following 72 h of treatment with Cpd3 (100 mg/kg body weight) in vivo. Data are presented as mean ± SD (n = 4 biological replicates). B Dosing and timing of allocated treatments for tumor-bearing mice. C CSC content following seven days of allocated treatments. CSCs were defined as CD133⁺ CD44⁺ cells or CD133⁺ CXCR4⁺ cells as assessed by flow cytometry. Data are presented as floating bars with lines indicating the median for n = 3 tumors per group and statistically analyzed using two-tailed t-tests to compare versus control. D Tumor growth in cm³ according to allocated treatments with two treatment cycles of 28 days each as outlined in (B), with n = 8–9 mice per group. Each mouse carried two tumors. Data are presented as mean ± SD. The arrows below depict treatment cycles, rather than specific treatment intervals or durations within each cycle. E Overall survival of tumor-bearing mice following allocated treatment. A total of 18 PDX models were treated using a 2 × 1 × 1 approach (two animals per model per treatment); n = 36 per group. F qPCR analysis of baseline NR5A2 and SOX2 mRNA levels (n = 8–10 biological replicates). Combined gene expression represents the mathematical product of NR5A2 and SOX2 mRNA levels. Data are presented as box and whisker plots with the center line denoting the median value. In panels A, D, and F data are statistically analyzed using two-tailed Mann–Whitney tests to compare two groups. Asterisks indicate significance at the indicated levels: * p < 0.05, ** p < 0.01, and *** p < 0.001. Please also see Supplementary Fig. 6