Main mechanisms involved in TME role in MDR are (i) abnormal tumor vasculature (promotion of angiogenesis and overexpression of VEGF), (ii) hypoxia, (iii) decreased pH (due to glycolysis), (iv) alterations in the expression of tumor suppressors and oncogenes [155,156,157,158] and (v) modulation of different signaling pathways (mTOR, ERK1/2) and growth-factors (FGF) [159]. This evidence concerns the gene MAPK3 and neoplasm.