Oliver's mTOR Atlas Evidence Platform
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Genome sequencing identifies a basis for everolimus sensitivity

Iyer G, Solit DB et al. · 2012 · Science · Atlas ID IYE2012

What this study shows

Genome sequencing of a single exceptional everolimus responder implicates TSC1 loss as the sensitivity basis. An n-of-1 observation, hypothesis-generating rather than confirmatory.

Abstract

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Cancer drugs often induce dramatic responses in a small minority of patients. We used whole-genome sequencing to investigate the genetic basis of a durable remission of metastatic bladder cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among the somatic mutations was a loss-of-function mutation in TSC1 (tuberous sclerosis complex 1), a regulator of mTOR pathway activation.

Read the full abstract on PubMed →

At a glance

Evidence type H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type3 - Human Observational
Model systemHuman (patient) + sequencing
JournalScience
Year2012
Peer reviewedYes
Record last updated2026-07-29
SourceDOI 10.1126/science.1226344 · PMID 22923433 · Free full text (PMC3633467)

Extracted findings

InterventionEverolimus (mTOR inhibitor)
TargetmTOR / TSC1
ModelHuman – metastatic bladder cancer patient + tumor sequencing
EffectLoss-of-function TSC1 mutation explains an exceptional everolimus response; TSC1 mutated in ~8% of bladder cancers
DoseEverolimus (mTOR inhibitor) in a phase II trial; whole-genome/targeted tumor sequencing of an exceptional responder.
Sample size1 exceptional responder + targeted sequencing of additional bladder tumors; 3 further TSC1-nonsense tumors identified (2 minor responders: 17% and 24% regression; 1 with 7%).
Effect sizeLoss-of-function TSC1 mutation underlies the exceptional everolimus response. TSC1-mutant tumors stayed on everolimus longer (7.7 vs 2.0 months, p=0.004) with improved time to recurrence (4.1 vs 1.8 months).
LimitationsInference from rare responders; basis of mTOR-inhibitor sensitivity beyond TSC1/2 loss still incompletely understood.

Cite this paper

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Iyer, G., et al. (2012). Genome sequencing identifies a basis for everolimus sensitivity. Science. https://doi.org/10.1126/science.1226344

@article{IYE2012,
  author       = {Iyer, G. and Solit, D. B. and others},
  title        = {{Genome sequencing identifies a basis for everolimus sensitivity}},
  journal      = {Science},
  year         = {2012},
  doi          = {10.1126/science.1226344},
  note         = {PMID: 22923433},
}

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 IYE2012) [Data set]. https://mtor-atlas.org/study/IYE2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_IYE2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record IYE2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/IYE2012/},
  doi          = {10.5281/zenodo.22059963}
}