Early Changes in [¹⁸F]FDG Uptake as a Readout for PI3K/Akt/mTOR Targeted Drugs in HER-2-Positive Cancer Xenografts

Figure 8

Schematic overview of the link between the PI3K/Akt/mTOR pathway and the Ras/MEK/ERK pathway. Growth factors bind receptor tyrosine kinases, which activate both the Ras/MEK/ERK and the PI3K/Akt/mTOR pathway, by regulating a cascade of phosphorylations. PI3K recruits and activates Akt on T308. Thereafter, phosphorylated Akt stimulates mTORC1 and mTORC2. Together with the phosphorylation of T308 by PI3K, S473 phosphorylation by mTORC2 is necessary for full Akt activation. After full activation of Akt, mTORC1 causes phosphorylation on T389 for pS6. mTORC1 initiates two negative feedback loops, firstly to Akt and secondly to IRS. Upon binding to receptor tyrosine kinases, the Ras/MEK/ERK pathway is also activated, eventually leading to activation of pS6 on S235/236. As known, activation of pS6 has an effect on cellular proliferation and glucose metabolism through upregulation of the expression of GLUT1.