mTOR kinase inhibitor potentiates apoptosis of PI3K and MEK inhibitors in diagnostically defined subpopulations.

Vijapurkar U, Robillard L, Zhou S, Degtyarev M, Lin K, Truong T, Tremayne J, Ross LB, Pei Z, Friedman LS, Blackwood EM, Belvin M.
Journal   Cancer Lett.
Species  
Analytes Measured   Akt , S6RP
Matrix Tested   Cell lysates
Year   2012
Volume   326
Page Numbers   168-75
Application   Phosphoproteins
Abstract
The mammalian target of rapamycin (mTOR) is a central node in a complex signaling network that is regulated by several pathways deregulated in human cancers, including the PI3K/Akt and MAPK pathways. Targeting mTOR therefore presents an opportunity for therapeutic intervention. However, mTOR inhibition with rapamycin analogs or kinase inhibitors reduces cell growth but does not induce apoptosis, and the clinical benefit of rapamycin analogs has been modest. In this study we show that mTOR kinase inhibitors can potentiate apoptosis when used in combination with upstream targeted agents such as PI3K and MEK inhibitors. This increased apoptosis is dependent on genetic background, and correlates with active growth factor survival pathways. In PI3K mutant tumors, mTOR inhibition leads to partial reactivation of Akt which allows cells to survive, whereas in KRAS mutant tumors, this same reactivation of Akt occurs but is not required for cell survival. These data suggest the use of selected rational combinations of mTOR kinase inhibitors with other targeted inhibitors in specific tumor genotypes to achieve the maximal cytotoxic response by inhibiting two nodes in the activated signaling network.

View Publications

Related Products

Phospho-Akt (Ser473) Kit
Akt | Human, Mouse, Rat, Non-human primate
Singleplex
Total Akt Kit
Akt | Human, Mouse, Rat, Non-human primate
Singleplex
Akt Control Pack 1
Akt
Akt Signaling Panel II Whole Cell Lysate Kit
Akt, GSK-3β, p70S6K, S6RP | Human, Mouse, Rat
Multiplex
Total S6RP Whole Cell Lysate Kit
S6RP | Human, Non-human primate, Mouse, Rat
Singleplex
Phospho(Ser240/244)/Total S6RP Whole Cell Lysate Kit
S6RP | Human, Mouse, Rat
Multiplex
Akt Signaling (Total Protein) Whole Cell Lysate Kit
Akt, GSK-3β, p70S6K | Human, Mouse, Rat
Multiplex
Phospho-S6RP (Ser240/244) Whole Cell Lysate Kit
S6RP | Human, Mouse, Rat
Singleplex
Akt Signaling Whole Cell Lysate Kit
Akt, GSK-3β, p70S6K | Human, Mouse, Rat
Multiplex
Phospho-Akt (Thr308) Whole Cell Lysate Kit
Akt | Human, Mouse
Singleplex
Phospho(Ser473)/Total Akt Whole Cell Lysate Kit
Akt | Human, Mouse, Rat
Multiplex
Phospho-Akt (Ser473) Antibody
Akt
Total Akt Antibody Bulk Product
Akt
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters