Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor

Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C, Banaji A, Won H, Wong W, Berger M, de Stanchina E, Barratt DG, …, Shokat KM · 2016 · Nature · Atlas ID ROD2016

What this study shows

RapaLink-1, a third-generation bivalent inhibitor, overcomes mTOR resistance mutations.

Abstract

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Precision medicines exert selective pressure on tumour cells that leads to the preferential growth of resistant subpopulations, necessitating the development of next-generation therapies to treat the evolving cancer. The PIK3CA-AKT-mTOR pathway is one of the most commonly activated pathways in human cancers, which has led to the development of small-molecule inhibitors that target various nodes in the pathway.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Cancer cells; mouse) 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 cells; mouse
Journal	Nature
Year	2016
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/nature17963 · PMID 27279227 · Free full text (PMC4902179)

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	New-generation bivalent mTOR inhibitor (RapaLink-type)
Target	mTOR (resistance mutations)
Model	Cancer cells; mouse
Effect	A bivalent next-generation inhibitor overcomes mTOR resistance mutations that defeat first- and second-generation drugs

In the Atlas

Cite this paper

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Rodrik-Outmezguine, V. S., Okaniwa, M., Yao, Z., Novotny, C. J., McWhirter, C., Banaji, A., Won, H., Wong, W., Berger, M., de Stanchina, E., Barratt, D. G., Cosulich, S., Klinowska, T., Rosen, N., & Shokat, K. M. (2016). Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. https://doi.org/10.1038/nature17963

@article{ROD2016,
  author       = {Rodrik-Outmezguine, V. S. and Okaniwa, M. and Yao, Z. and Novotny, C. J. and McWhirter, C. and Banaji, A. and Won, H. and Wong, W. and Berger, M. and de Stanchina, E. and Barratt, D. G. and Cosulich, S. and Klinowska, T. and Rosen, N. and Shokat, K. M.},
  title        = {{Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor}},
  journal      = {Nature},
  year         = {2016},
  doi          = {10.1038/nature17963},
  note         = {PMID: 27279227},
}

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 ROD2016) [Data set]. https://mtor-atlas.org/study/ROD2016/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ROD2016,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ROD2016},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ROD2016/},
  doi          = {10.5281/zenodo.22059963}
}

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