Figure 7: Inhibition of ERRα impairs the growth of lapatinib-resistant tumours.

(a) Lapatinib-naive murine ErbB2-driven mammary tumours were transplanted into the mammary fat pads of MMTV-Cre mice. Growth curves indicate the response of the tumours to vehicle (n=8), C29 monotherapy (n=9), lapatinib monotherapy (n=12) and lapatinib/C29 combination therapy (n=10). *P<0.05, one-way analysis of variance (ANOVA) with Tukey’s post-test. (b) Quantification of the therapeutic response and recurrence in response to sustained treatment with lapatinib and C29 individually and in combination. Partial or no response was defined as no effect of treatment on tumour growth or a reduced rate of growth with incomplete tumour regression. Complete response was defined as total regression of the tumour mass to a non-palpable state. Recurrence was defined as the regrowth of any palpable tumour mass within the follow-up period of 20 weeks. (c) A lapatinib-resistant murine ErbB2-driven mammary tumour was transplanted into the mammary fat pads of MMTV-Cre mice. Growth curves indicate the response of the tumours to lapatinib monotherapy (n=8) and lapatinib/C29 combination therapy. **P<0.01, one-way ANOVA with Tukey’s post-test. Box plot shows the tumour size for both treatment groups at the end of the experiment. P value was generated by comparing the mean tumour size using an unpaired Student’s t-test. (d) A working model of the role of the mTOR-ERRα axis in dictating the metabolic response of ERBB2-driven breast cancer cells to lapatinib and the potential for ERRα antagonists to counteract lapatinib resistance in those cells.