Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer

Numerous studies have established a causal link between aberrant mammalian target of rapamycin (mTOR) activation and tumorigenesis, indicating that mTOR inhibition may have therapeutic potential. In this study, we show that rapamycin and its analogs activate the MAPK pathway in human cancer, in what represents a novel mTORC1-MAPK feedback loop. We found that tumor samples from patients with biopsy-accessible solid tumors of advanced disease treated with RAD001, a rapamycin derivative, showed an administration schedule-dependent increase in activation of the MAPK pathway.

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Carracedo, A., et al. (2008). Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. The Journal of clinical investigation. https://doi.org/10.1172/JCI34739

@article{CAR2008,
  author       = {Carracedo, A. and Pandolfi, P. P. and others},
  title        = {{Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer}},
  journal      = {The Journal of clinical investigation},
  year         = {2008},
  doi          = {10.1172/JCI34739},
  note         = {PMID: 18725988},
}

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 CAR2008) [Data set]. https://mtor-atlas.org/study/CAR2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_CAR2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record CAR2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/CAR2008/},
  doi          = {10.5281/zenodo.22059963}
}