page_title: MTOR inhibitors
section_title: Effects on tumor angiogenesis
hierarchical_section_title: MTOR inhibitors / Mechanism of action / Effects on tumor angiogenesis
caption_attribution_description: English: Mechanism of action of Rapamycin and its derivatives on tumor angiogenesis.
context_page_description: mTOR inhibitors are a class of drugs that inhibit the mammalian target of rapamycin, which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase related kinases. mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs, which have shown tumor responses in clinical trials against various tumor types.
context_section_description: Tumor angiogenesis rely on interactions between endothelial vascular growth factors which can all activate the PI3K/AKT/mTOR in endothelial cells, pericytes, or cancer cells. Example of these growth factors are angiopoietin 1 (ANG1), ANG 2, basic fibroblast growth factor (bFGF), ephrin-B2, vascular endothelial growth factor (VEGF), and members of the tumor growth factor-β (TGFβ) superfamily. One of the major stimuli of angiogenesis is hypoxia, resulting in activation of hypoxia-inducible transcription factors (HIFs) and expression of ANG2, bFGF, PDGF, VEGF, and VEGFR. Inhibition of HIF1α translation by preventing PDGF/PDGFR and VEGF/VEGFR can result from mTOR inhibition. A G0-G1 cell-cycle blockage can be the consequence of inactivation of mTOR in hypoxia-activated pericytes and endothelial cells. 
  There are some evidence that extended therapy with rapamycin may have effect on AKT and mTORC2 as well.
caption: Effects of rapamycin and rapalogs on endothelial and tumor cells
exif: {}