Fig. 1.

OS of mice bearing bioassay positive platinum-resistant or sensitive human HGSCs improved with birinapant and carboplatin co-administration. a Schema of in vitro organoid bioassay. Organoids treated with drug for 72 h were released, dissociated, and analyzed for survival by flow cytometry and passaging. Sensitivity to co-therapy was defined as ≤1% survival and no growth after passaging. b Graph showing the percentage of cells that survived treatment. Co-therapy sensitive lines S9-GODL and S1-GODL were eliminated, while co-therapy resistant lines S8-GODL and Ovcar-3 survived co-therapy. Results are mean ± SD, n = 3 replicates/cell line. c Experimental schema to assess the in vivo efficacy of birinapant and carboplatin co-therapy. Mice bearing IP human HGSCs were randomized to receive a 4-week course of vehicle, birinapant, carboplatin, or the combination of birinapant and carboplatin (n = minimum 8/arm). Mice were euthanized when they met NIH-defined endpoint criteria. d OS increased in mice bearing S9-GODL and S1-GODL tumors. (i) Co-therapy significantly increased OS in mice bearing platinum-resistant S9-GODL HGSC tumors (p < 0.0001, co-therapy vs. carboplatin). (ii) Co-therapy did not impact survival of mice bearing platinum-resistant S8-GODL tumors (p = 0.0753, co-therapy vs. carboplatin). (iii) Mice bearing platinum-sensitive S1-GODL tumors had increased OS with co-therapy (p = 0.01, co-therapy vs. carboplatin). (iv) Co-therapy did not improve OS in mice bearing Ovcar-3 tumors (p = 0.2340, co-therapy vs. carboplatin)