Fig. 3: Combination of PKMYTi-ATRi synergistically suppress CCNE1 amplified OVCA and EMCA PDXs growth.
From: Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR
A–C Tumor volume growth was measured weekly in (A) EMCA WU-115 (B) OVCA WO-19, and (C) OVCA WO-77 CCNE1 amplified PDX models treated with the indicated drugs. RP-6306 was given oral BID on days 1–5, and RP-3500 was given oral QD on 3 days on / 4 days off schedule until tumor progression (tumor volume > 1000 mm3). Survival rate (middle panel) and metastases (right panel) was analyzed at the end of each experiment. Metastases was defined as the number of organs with metastatic disease in each mouse. D The toxicity of drugs was revealed by the mice body weights changes. E Tumor growth (left) and body weight change (right) of OVCAR3 xenografts in mice treated with either RP-6306, RP-3500, or both. RP-3500 was given oral QD, and RP-6306 was given oral BID, both given on a 3-day on / 4-day off schedule for 24 days (n = 8). Tumor growth and percent body weight change shown is mean ± SEM. Longitudinal tumor growth was analyzed by linear mixed effects modeling with type II ANOVA and pairwise comparisons across groups. Data were analyzed for overall survival using the Mantel-Cox log-rank test. Metastases were compared with one-way ANOVA followed by Tukey’s multiple comparisons. The body weight shown is mean ± SEM.
