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Published on: September 19, 2018
Application of pharmacologically induced transcriptomic profiles to interrogate PI3K-Akt-mTOR pathway activity
Matthew H Ung1, George L Wang1, Frederick S Varn1
1Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, 03755 USA.
Abstract:
The PI3K-Akt-mTOR signaling pathway has been identified as a key driver of carcinogenesis in several cancer types. As such, a major area of focus in cancer biology is the development of genomic biomarkers that can measure the activity level of the PI3K-Akt-mTOR pathway. In this study, we systematically estimate PI3K-Akt-mTOR pathway activity in breast primary tumor samples using transcriptomic profiles derived from drug treatment in MCF7 cell lines. We demonstrate that gene expression profiles derived from chemically-induced protein inhibition allows us to measure PI3K-Akt-mTOR pathway activity in patient tumor samples. With this approach, we predict prognosis and response to chemotherapy in cancer patients, and screen for potential pharmacological modulators of PI3K-Akt-mTOR pathway inhibitors.
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