The multiple biologic effects of mTOR – Target mTOR

The multiple biologic effects of mTOR – Target mTOR

mTOR—an important factor driving aRCC progression^1-7

Cell growth and proliferation and mTOR

• mTOR controls the cell's translational machinery (eg, ribosomes) and the production of proteins^8,13:
  • Necessary for progress through the cell cycle
  • Essential for cell growth

Metabolism and mTOR

• Many cancer cells rely on glycolysis—not oxidative phosphorylation—for energy^14,15
• Activated mTOR increases production of the enzymes necessary for glycolysis and controls the uptake of glucose and other nutrients^9,15,16
• Increased glucose uptake and metabolism helps fulfill the energy needs for mTOR-driven cell growth and proliferation^9,16

Angiogenesis and mTOR

• Activated mTOR stimulates HIF and VEGF^7,8,12,17
• 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