Targeting PI3K/Akt/mTOR signaling:
The shutdown of cell survival signaling

Phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) comprise 3 major junctions in the PI3K/Akt/mTOR signaling pathway and are typically activated by upstream signaling of tyrosine kinases and other receptor molecules.¹ PI3K is the subject of extensive research at Genentech, a member of the Roche Group.

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Class IA PI3Ks are a subgroup of the PI3K family that are activated by receptor tyrosine kinases.¹ Their primary role is to convert PIP₂ to PIP₃.¹ Akt is activated following recruitment to the cell surface by PIP₃ and acts downstream of PI3K to regulate many cellular processes, including cell survival, proliferation, and growth.¹ mTOR is a key protein in the pathway that acts both upstream and downstream of Akt.¹ mTOR is active in 2 different multiprotein complexes, TORC1 and TORC2, and regulates protein synthesis necessary for cell growth, proliferation, angiogenesis, and other cellular endpoints.^1-3

Activation of the PI3K/Akt/mTOR signaling pathway regulates¹:

• Cell growth
• Cell proliferation
• Cell survival

References:

1.

Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase-AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489-501.

2.

Bhaskar PT, Hay N. The two TORCs and Akt. Dev Cell. 2007;12:487-502.

3.

Lee DF, Hung MC. All roads lead to mTOR: integrating inflammation and tumor angiogenesis. Cell Cycle. 2007;6:3011-3014.