Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence

Figure 3

Schematic representation showing paths and points of action of the mTOR kinase domain inhibitors (AZD8055 (AstraZeneca) and OSI-027 (OSI Pharmaceuticals)) currently evaluated in clinical trials. Legend: PI3K: phosphatidylinositol-3-kinase; PIP2: phosphatidylinositol (4,5)-bisphosphate; PIP3: phosphatidylinositol (3,4,5)-trisphosphate; PTEN: phosphatase and tensin homolog; AKT: protein kinase B; TSC1/2: tuberous sclerosis complex 1/2; GTP: guanosine triphosphate; RHEB: RAS homolog enriched in brain; mTOR: mechanistic target of rapamycin; RAPTOR: regulatory-associated protein of mTOR; PRAS40: proline-rich AKT substrate 40 kDa; mLST8: mammalian lethal with Sec-13 protein 8; DEPTOR: DEP domain TOR-binding protein; RICTOR: rapamycin-insensitive companion of mTOR; PROTOR: protein observed with RICTOR; mSIN1: stress-activated map kinase-interacting protein 1; FKBP12: 12-kDa intracellular FK506-binding protein; rapalogs: rapamycin analogs; FATC: FAT carboxyl terminal; FRB: FKBP-rapamycin-binding domain.