Fig. 2

Cediranib combined with olaparib reduces tumor dissemination and prologs survival in orthotopic OC-PDXs. Drug effect in orthotopic OC-PDXs. Olaparib (100 mg/kg) and cediranib (3 mg/kg), monotherapy or combined, were given orally by gavage QD (Q1 × 5) until progression. Left panels: Survival (Kaplan Meier) curves of tumour bearing mice; the benefit calculated as increment of lifespan (ILS%) of disease bearing mice is indicated. Coloured bars at the bottom indicate the study dosing period. DDP response is reported in insert at the side. Right panels: Abdominal tumour burden (i.e. volume of ascites in the peritoneal cavity and organ dissemination) assessed after 4 weeks of treatment. Ascites and dissemination data are mean ± SD. “Random” indicates tumour burden at randomization (start of treatment). Statistic by Wilcoxon rank-sum test/log-rank test (left panels) or ANOVA and Tukey’s post-test (right panels). *P < 0.05; **P < 0.01; ***P < 0.005; ****P < 0.001; *****P < 0.0001. A MNHOC8 (wild-type for BRCA genes Additional file 1: Fig. S1B but lacking BRCA1 mRNA due to promoter methylation Additional file 1: Fig. S3): mice were randomized 7 days after intraperitoneal tumor transplant. Vehicle N = 9, CED N = 12, OLA N = 12, OLA + CED N = 6. B MNHOC506 (wild-type for HRR genes; Additional file 1: Fig. S1B): mice were randomized 9 days after intraperitoneal tumor transplant. Vehicle N = 7, CED N = 7, OLA N = 7, OLA + CED N = 8. Representative images of tumor dissemination in liver are reported. C MNHOC22 (carrying a homozygous pathogenic nonsense mutation in BRCA1, truncating the protein; Additional file 1: Fig. S1): mice were randomized 6 days after intraperitoneal tumor transplant. Vehicle N = 13, CED N = 9, OLA N = 13, OLA + CED N = 9. (Detailed methods in Additional file 2)