ArticleCancer discovery2014
A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 276 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
276 citing papers in PubMed, 451 citations in OpenAlex.
- Exemestane plus everolimus and palbociclib in metastatic breast cancer: clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial.Nature communications · 2024Trial
- A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161.Investigational new drugs · 2022Trial
- Molecular Characterization and Prospective Evaluation of Pathologic Response and Outcomes with Neoadjuvant Therapy in Metaplastic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Autophagy Inhibition to Augment mTOR Inhibition: a Phase I/II Trial of Everolimus and Hydroxychloroquine in Patients with Previously Treated Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Cancer treatment alters mutant selection in normal esophagus.Nature genetics · 2026Article
- Mutational patterns in a large cohort of parathyroid carcinomas.Journal of endocrinological investigation · 2026Article
- Translational resistance to amino acid starvation in breast cancer cells revealed by ribosome profiling.iScience · 2026Article
- Divergent signaling profiles in mTOR gain-of-function Smith-Kingsmore syndrome (SKS) and TSC2 deficiency.bioRxiv : the preprint server for biology · 2026Article
- Causal links of 233 metabolic markers to benign prostatic hyperplasia: Mendelian randomization and RNA-sequencing insights.Journal of the Chinese Medical Association : JCMA · 2026Article
- Integration of gene expression profiling and mutation analysis via RNA sequencing: transitioning the 95-gene classifier to a next-generation platform in early-stage HR+/HER2- breast cancer.Breast cancer (Tokyo, Japan) · 2026Article
- mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Signaling to make human ribosomes: Connections between the cytoplasm and the nucleolus.Molecular cell · 2026Review
- Evolutionary Divergence of mTOR-mediated Transcriptional Regulation BetweenbioRxiv : the preprint server for biology · 2026Article
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- Telomeric autophagy in human health, aging, and diseases.Frontiers in molecular biosciences · 2026Review
- GATOR1 complex controls cisplatin sensitivity.Cell death & disease · 2025Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Comprehensive characterization and targeted treatment of a pediatric epithelioid glioblastoma with a rare TRIM24-NTRK2 fusion.NPJ precision oncology · 2025Article
- System analysis links SMARCD3 regulons to growth signaling and MEK inhibitor response in everolimus-resistant ER+ breast cancer cells.Cell reports. Medicine · 2025Article
- Article
216 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 1 country.
Funding
Abstract
Genes encoding components of the PI3K-AKT-mTOR signaling axis are frequently mutated in cancer, but few mutations have been characterized in MTOR, the gene encoding the mTOR kinase. Using publicly available tumor genome sequencing data, we generated a comprehensive catalog of mTOR pathway mutations in cancer, identifying 33 MTOR mutations that confer pathway hyperactivation. The mutations cluster in six distinct regions in the C-terminal half of mTOR and occur in multiple cancer types, with one cluster particularly prominent in kidney cancer. The activating mutations do not affect mTOR complex assembly, but a subset reduces binding to the mTOR inhibitor DEPTOR. mTOR complex 1 (mTORC1) signaling in cells expressing various activating mutations remains sensitive to pharmacologic mTOR inhibition, but is partially resistant to nutrient deprivation. Finally, cancer cell lines with hyperactivating MTOR mutations display heightened sensitivity to rapamycin both in culture and in vivo xenografts, suggesting that such mutations confer mTOR pathway dependency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.