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Review
. 2012 Dec;17(3-4):205-16.
doi: 10.1007/s10911-012-9264-2. Epub 2012 Aug 4.

Targeting the PI3K/Akt/mTOR pathway for breast cancer therapy

Justin Cidado  1 , Ben Ho Park
Affiliations
Review

Targeting the PI3K/Akt/mTOR pathway for breast cancer therapy

Justin Cidado et al. J Mammary Gland Biol Neoplasia. 2012 Dec.

Abstract

Recent advances in genetics and genomics have revealed new pathways that are aberrantly activated in many breast cancers. Chief among these genetic changes are somatic mutations and/or gains and losses of key genes within the phosphoinositide 3-kinase (PI3K) pathway. Since breast cancer cell growth and progression is often dependent upon activation of the PI3K pathway, there has been intense research interest in finding therapeutic agents that can selectively inhibit one or more constituents of this signaling cascade. Here we review key molecules involved with aberrant PI3K pathway activation in breast cancers and current efforts to target these components for therapeutic gain.

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Figures

Figure 1
Figure 1
The PI3K/Akt/mTOR pathway. Activation of a receptor tyrosine kinase (RTK) leads to increased activity of PI3 kinase complexes (p85 and p110) which in turn converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3); a reaction that is antagonized by the tumor suppressor Pten. PIP3 then phosphorylates and activates Akt, which through a series of subsequent phosphorylation events leads to activation of the mTOR complexes, mTORC1 and mTORC2. mTOR complexes are also kinases that activate via phosphorylation substrates such as S6 and 4E-BP1 that increase transcription of growth promoting genes. Points of pharmacologic inhibition that are currently the focus of drug development are shown.
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