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Oncotarget. 2016 Dec 20;7(51):84142-84154. doi: 10.18632/oncotarget.11776.

Application of pharmacologically induced transcriptomic profiles to interrogate PI3K-Akt-mTOR pathway activity associated with cancer patient prognosis.

Author information

1
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, 03755 USA.
2
Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, 03755 USA.
3
Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, 03766 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.

KEYWORDS:

PI3K; computational biology; drug treatment; pharmacogenomics

PMID:
27589846
PMCID:
PMC5356650
DOI:
10.18632/oncotarget.11776
[Indexed for MEDLINE]
Free PMC Article

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