Figure 3.

(A) qRT-PCR performed on tumour mRNA indicated greater than two-fold induction of VEGF-related transcripts during response phase (T1 vs pre) (white bars). During escape phase (T2 vs T1) (black bars) several pro-angiogenic transcripts were induced greater than two-fold. All changes in expression levels between response and escape phases were significant (n=4, P<0.01, t-test) except MEK1 and ERK1 (P>0.05). (B) Combination treatment of mice bearing Ren-02 tumours with continuous sunitinib (40 mg kg⁻¹ day⁻¹) (□), continuous sunitinib+continuous MEK inhibitor (PD-325901) (4 mg kg⁻¹ day⁻¹) (▪), MEK inhibitor added to sunitinib on d30 (▵), or sunitinib switched to MEK inhibitor on d30 (O). Tumour growth was reduced with the addition of a MEK inhibitor on d30 (P=0.0054), and even further reduced by continuous MEK inhibitor therapy (P=0.0241) or switching to MEK inhibitor monotherapy on d30 (P=0.0068). Continuous combination treatment (▪) was not statistically different from switching from sunitinib to MEK inhibitor (O) (P=0.076).