The multiple biologic effects of mTOR – Target mTOR

The multiple biologic effects of mTOR – Target mTOR

mTOR—an important factor driving aRCC progression1-7

Cell growth and proliferation and mTOR

  • mTOR controls the cell's translational machinery (eg, ribosomes) and the production of proteins8,13:
    • Necessary for progress through the cell cycle
    • Essential for cell growth

Metabolism and mTOR

  • Many cancer cells rely on glycolysis—not oxidative phosphorylation—for energy14,15
  • Activated mTOR increases production of the enzymes necessary for glycolysis and controls the uptake of glucose and other nutrients9,15,16
  • Increased glucose uptake and metabolism helps fulfill the energy needs for mTOR-driven cell growth and proliferation9,16

Angiogenesis and mTOR

  • Activated mTOR stimulates HIF and VEGF7,8,12,17
  • Activated mTOR also stimulates VEGF-independent angiogenic processes
    • The proliferation of blood vessel cells8
    • The proliferation of pericytes that help stabilize tumor blood vessels8
    • The production of the proangiogenic factor FGF (fibroblast growth factor)18-20

Inhibit mTOR—An important target with multiple biologic effects

  • mTOR inhibition limits a tumor's ability to grow and spread by reducing*7-13,18-20:
    • Cell growth and proliferation
    • Cell metabolism
    • Both VEGF-dependent and VEGF-independent tumor angiogenesis
    • Dual cell targets: inhibit mTOR in both tumor and blood vessel cells12