Targeting metabolic symbiosis to overcome resistance to anti-angiogenic therapy

Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. In the present study, we aimed to identify resistance mechanisms to the small-molecule tyrosine kinase inhibitor nintedanib in the Py2T murine breast cancer transplantation model. To identify differences in gene expression between short- and long-term nintedanib and untreaded FAC-sorted tumor and endothelial cells, we performed gene expression profiling by using affymetrix microarrays. The murine breast cancer cell line Py2T was injected into a mammary fat pad of FVB/N mice. Treatment with nintedanib was initiated when tumors reached a measurable size. After 1 week (short-term treatment) and 3 weeks of nintedanib treatment (long-term treatment), treated and untreated control (size-matched to the long-term nintedanib treatment group) tumor and endothelial cells were FAC-sorted, RNA was extracted and hybridized on Affymetrix microarrays.