Figure 7
DIACC3010 and trastuzumab, alone and in combination, had differential effects in a panel of GC patient-derived xenograft models. (a-d) nu/nu mice bearing subcutaneous PDX tumors (100–250 mm3) were treated (n = 3 per group) with vehicle control, DIACC3010 (20 mg/kg QD po), trastuzumab (15 mg/kg QW iv), or a combination of DIACC3010 + trastuzumab, with the exception of GAX059 and GAX066 models, which received DIACC3010 at 30 mg/kg QD po. TVs and body weights were measured twice per week and the study was terminated when mean TV in the vehicle control group reached 1200 mm3. (a) Treatment with DIACC3010 alone and combined with trastuzumab significantly inhibited tumor growth compared with vehicle control in 4 models but these 2 treatments were not significantly different from each other. (b) Treatment with trastuzumab alone and combined with DIACC3010 significantly inhibited tumor growth compared to vehicle control in 3 models but these 2 treatments were not significantly different from each other. (c) Treatment with both agents alone and in combination all inhibited tumor growth equally compared to vehicle control in 5 models. (d) The combination of DIACC3010 + trastuzumab significantly inhibited tumor growth in 2 models compared to vehicle control, whereas effects of the monotherapies were not significant. In the GAX007 models, the combination effects on tumor growth were significantly different from the monotherapy effects. The model names, mutated oncogenic hotspot genes, and HER2 status are given above each graph. A lack of given HER2 status means the model was HER2 (1+) or (0). a,b,cTumor volume means of treatment groups for each model with similar superscripts were not significantly different (a = 0.10).
