Figure 1.

Trastuzumab (Trast) plus a γ-secretase inhibitor (GSI) prevents or reduces tumour recurrence. ErbB-2-overexpressing BT474 xenografts were generated in 56 ovariectomised, athymic nude mice by injecting 5 × 10⁶ cells into both mammary fat pads. Once tumours reached a mean tumour cross-sectional area of 0.20 cm², mice were randomised and treated with vehicle (100 μl sterile PBS injected i.p. 1 day per week and 200 μl 2% carboxymethylcellulose), 10 mg kg⁻¹ trastuzumab in 100 μl PBS injected i.p. once weekly, 5 mg kg⁻¹ LY 411 575 GSI (A) or 100 mg kg⁻¹ MRK-003 GSI (B) in 200 μl 2% carboxymethylcellulose, fed by oral gavage, three days on, 4 days off, or trastuzumab plus LY 411 575 GSI or MRK-003 GSI. Tumour area (length × width) was measured weekly using Vernier calipers. The measurements were performed up to 12 or 19 weeks. The treatments were stopped and tumour recurrence was measured up to an additional 105 days or 98 days in mice that specifically showed complete tumour regression (A and B). Results from (A and B) show mean tumour cross-sectional area ((area × Π)/4) on the y axis and time in weeks on the x axis. Error bars are s.d. of the mean for 12 mice bearing tumours in the response phase of the study and 8 mice for the recurrent phase of the study. The results from (A and B) also demonstrate mice bearing recurrent tumours on the y axis and treatments on the x axis. ^*Statistically significant differences between mean slopes of the curve for trastuzumab plus GSI vs GSI alone. ^**Statistically significant differences between mean slopes of the curve for trastuzumab vs trastuzumab plus GSI in recurrent tumours. Linear regression analyses were performed for tumour growth curves in (A and B).