Neal Rosen
Showed that blocking mTORC1 releases a feedback brake on receptor tyrosine kinases and AKT, explaining how tumours escape mTOR and PI3K inhibitors and shaping how these drugs are combined in the clinic
Member Emeritus, MSKCC · fellowship, NCI · residency, Brigham and Women's Hospital · MD, PhD, Albert Einstein College of Medicine
Rosen Lab (Member Emeritus), Memorial Sloan Kettering Cancer Center (New York, New York, USA) ↗
Portrait: Memorial Sloan Kettering Cancer Center
In 2006 (ORE2006), showed mTOR inhibition paradoxically activates upstream RTK/Akt signaling via feedback release — foundational explanation for why single-agent mTOR inhibitors often fail. As senior author on ROD2011, extended this to mTOR-kinase inhibitors.
This 'feedback reactivation' framework became a central organizing principle of modern targeted-therapy combinations. NIH/NCI Outstanding Investigator Award (2016); AACR Academy Fellow (2022).
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2006 | M | mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt ORE2006 mTOR inhibition relieves feedback suppression of RTK signaling, paradoxically activating Akt. |
| 2011 | M | mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling ROD2011 Senior author: mTOR-kinase inhibitors cause feedback-dependent biphasic AKT rebound. |
| 2016 | M | Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor ROD2016 RapaLink-1, a third-generation bivalent inhibitor, overcomes mTOR resistance mutations. |
Co-authors in the Atlas 5
People with a profile here who share at least one study with Neal Rosen.
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- José Baselga 2 shared studies Breast cancer oncologist who led the BOLERO-2 trial showing that the mTOR inhibitor everolimus added to hormone therapy lengthens progression-free survival
- Vanessa S. Rodrik-Outmezguine 2 shared studies Showed that tumours reactivate AKT after mTOR kinase inhibition, and that the third-generation inhibitor RapaLink-1 overcomes mTOR resistance mutations
- Kathryn O'Reilly Physician-scientist who, in Neal Rosen's lab at Memorial Sloan Kettering, showed that blocking mTORC1 with rapamycin-like drugs switches on the survival kinase Akt through a feedback loop, a main reason these drugs worked less well against cancer than hoped
- Kevan M. Shokat Co-developed the ATP-competitive 'TORKinib' mTOR inhibitors that block both mTORC1 and mTORC2, and later, with Neal Rosen's lab at Memorial Sloan Kettering, RapaLink-1, a third-generation inhibitor that overcomes mTOR resistance mutations
- Sabina Cosulich Cancer drug discovery scientist at AstraZeneca whose work spans PI3K and mTOR pathway inhibitors, PARP1 inhibitors and phosphoinositide lipid signalling
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