mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt

O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N · 2006 · Cancer research · Atlas ID ORE2006

What this study shows

mTORC1 inhibition relieves feedback and activates upstream RTK-PI3K-Akt signalling. The Akt activation was demonstrated both in cancer cell lines and in patient tumours treated with RAD001 (everolimus), so this record carries a human pharmacodynamic component, not only in-vitro data.

Abstract

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Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent loss in insulin receptor substrate-1 expression leading to feedback down-regulation of signaling through the pathway. In model systems, tumors exhibiting mutational activation of phosphoinositide-3-kinase/Akt kinase, a common event in cancers, are hypersensitive to mTOR inhibitors, including rapamycin.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Cancer cell lines + patient tumours treated with the rapamycin derivative RAD001 (everolimus)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Cancer cell lines + patient tumours treated with the rapamycin derivative RAD001 (everolimus)
Journal	Cancer research
Year	2006
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1158/0008-5472.CAN-05-2925 · PMID 16452206 · Free full text (PMC3193604)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	mTOR inhibition (rapamycin)
Target	mTOR / IRS-1 / Akt / RTK
Model	Cancer cell lines and patient tumours (RAD001/everolimus-treated)
Effect	mTOR inhibition relieves S6K1-IRS1 feedback and induces upstream RTK signalling, activating Akt (a resistance mechanism). Shown in cancer cell lines AND confirmed in patient tumours treated with RAD001 - a human pharmacodynamic readout, not only cell culture.

In the Atlas

Links in the pathway map

Supports S6K1 inhibits IRS-1 / IRS-2

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Cite this paper

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O'Reilly, K. E., Rojo, F., She, Q. B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., Baselga, J., & Rosen, N. (2006). mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer research. https://doi.org/10.1158/0008-5472.CAN-05-2925

@article{ORE2006,
  author       = {O'Reilly, K. E. and Rojo, F. and She, Q. B. and Solit, D. and Mills, G. B. and Smith, D. and Lane, H. and Hofmann, F. and Hicklin, D. J. and Ludwig, D. L. and Baselga, J. and Rosen, N.},
  title        = {{mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt}},
  journal      = {Cancer research},
  year         = {2006},
  doi          = {10.1158/0008-5472.CAN-05-2925},
  note         = {PMID: 16452206},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record ORE2006) [Data set]. https://mtor-atlas.org/study/ORE2006/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ORE2006,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ORE2006},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ORE2006/},
  doi          = {10.5281/zenodo.22059963}
}

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