mTOR Overview

mTOR: A Central Regulator Of Cell Proliferation, Angiogenesis, and Cell Metabolism

mTOR is a kinase protein predominantly found in the cytoplasm of the cell. It acts as a central regulator of many biological processes that are essential for cell proliferation, angiogenesis, and cell metabolism.^1-3 mTOR exerts its effects primarily by turning on and off the cell's translational machinery, which includes the ribosomes, and is responsible for protein synthesis.¹

The location and role of mTOR in the cell.

mTOR is a key intracellular point of convergence for a number of cellular signaling pathways. mTOR performs its regulatory function in response to activating or inhibitory signals transmitted through these pathways, which are located upstream from mTOR in the cell. These diverse signaling pathways are activated by a variety of growth factors (including vascular endothelial growth factors (VEGFs), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1)), hormones (estrogen, progesterone), and the presence or absence of nutrients (glucose, amino acids) or oxygen.^4,5

One or more of these signaling pathways may be abnormally activated in patients with many different types of cancer, resulting in deregulated cell proliferation, tumor angiogenesis, and abnormal cell metabolism.^1,4,5

mTOR is an important therapeutic target because:

• It is a key intracellular point of convergence for a number of signaling pathways that are abnormally activated in many types of cancer^1,4
• It appears to be a stable target that does not mutate^1,5,6
• Inhibiting mTOR:
  • May inhibit abnormal cell proliferation, tumor angiogenesis, and abnormal cell metabolism
  • May potentially enhance the efficacy of other cancer treatments^{1, 5, 7}