Our findings point out the need to consider the crucial role of tumor stroma heterogeneity in cancer progression, in particular the role played by mesenchymal to amoeboid transition in endothelial cells, thereby how their plasticity can contribute to tumor angiogenesis in a unique way that limited the efficacy of MPIs and still limits the effectiveness of Bevacizumab therapy due to their unresponsive to VEGF. The gene discussed is VEGFA; the disease is neoplasm.