Taken together, our data indicate that intrinsic bevacizumab-resistance is multifactorial and associated with i) the high levels of VEGF in the tumor environment that renders the endothelial cells more resistant to bevacizumab, ii) strong VEGFR1 and VEGFR2 signaling in the tumor cells that leads to mTORC1 activation as well as iii) resistance to hypoxia-induced apoptosis. The gene discussed is VEGFA; the disease is neoplasm.