Since several reports show metformin-mediated reduction of VEGFR function in both preclinical [47-49] and in mice fed a high fat diet and clinically in polycystic ovarian syndrome (PCOS) and type 2 diabetes settings [50-52], inhibiting both systems- VEGFR function by metformin and CXCR4/CXCL12 by plerixafor, might be required to achieve a durable antitumor response. This evidence concerns the gene CXCL12 and polycystic ovary syndrome.