Systematic name M16515
Brief description Genes in the AKT1 [GeneID=207] pathway which are independent of MTOR [GeneID=2475], insensitive to RAD001 (everolimus) [PubChem=6442177].
Full description or abstract The Akt pathway is commonly deregulated in many cancers. Clinical trials are currently underway to test the effectiveness of breast cancer treatment by inhibition of various Akt pathway intermediates. A set of genes induced by Akt in a transgenic mouse model, a subset of which were sensitive to mammalian target of rapamycin (mTOR) inhibitor RAD001, was examined in five public gene expression profile data sets of clinical breast tumor specimens (representing >1000 different samples in all). In each of the clinical data sets, the Akt mouse model genes as a group were significantly overexpressed in human tumors having high levels of AKT1 mRNA. The subset of genes both upregulated by Akt and dependent on mTOR activity were associated with estrogen receptor-negative status, higher grade, increasing tumor size and poor prognosis in multiple patient cohorts; these associations were either not present or not as strong for the Akt-induced, mTOR-independent genes or for AKT1 expression alone. The genes shown here to be relevant to Akt-mTOR both experimentally and pathologically have the potential for use in a molecular diagnostic to determine which patients should receive mTOR antagonist treatment.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17213801   Authors: Creighton CJ
Exact source Table 1: RAD001-insensitive
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform Human_NCBI_Gene_ID
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Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
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Version history 3.0: First introduced

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