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mTOR and cancer: insights into a complex relationship
Abstract
mTOR (mammalian target of rapamycin) has come a long way since its humble beginnings as a kinase of unknown function. As part of the mTORC1 and mTORC2 complexes mTOR has key roles in several pathways that are involved in human cancer, stimulating interest in mTOR inhibitors and placing it on the radar of the pharmaceutical industry. Here, I discuss the rationale for the use of drugs that target mTOR, the unexpectedly complex mechanism of action of existing mTOR inhibitors and the potential benefits of developing drugs that function through different mechanisms. The purpose is not to cover all aspects of mTOR history and signalling, but rather to foster discussion by presenting some occasionally provocative ideas.
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“Similarly, the use of the TOR inhibitor rapamycin is currently being actively pursued as a treatment for human malignancies 85 .”
From The common biology of cancer and ageing (2007) · cites this paper as [85]
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“For our purpose, suffice it to say that TOR is activated in the presence of abundant nutrients, and inactivated under starvation.”
From The common biology of cancer and ageing (2007) · cites this paper as [85]
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Targeted Inhibition of Angiogenic Factors in AIDS-related Disorders
Aoki, Y., & Tosato, G. (2003) · Current Drug Targets - Infectious Disorders · doi:10.2174/1568005033481222 · Cited by 25
Flagged first, then by citations
1 of the 94 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
AKT/PKB signaling: navigating downstream
Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115
Cillà, S. D., Farruggio, S., Vujosevic, S., Raina, G., Filippini, D. A., Gatti, V., Clemente, N., Mary, D., Vezzola, D., Casini, G., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479441 · Cited by 5,154
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Autophagy: cellular and molecular mechanisms
Glick, D. R., Barth, S., & Macleod, K. F. (2010) · The Journal of Pathology · doi:10.1002/path.2697 · Cited by 3,995
Targeting the phosphoinositide 3-kinase pathway in cancer
Liu, P., Cheng, H.-L. M., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,785
Metadata
- Authors
- Sabatini, D. M.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Sabatini, David M.
- ORCID
- Sabatini, David M.
- Venue
- Nature Reviews Cancer
- Published
- 2006-08-17
- Volume
- 6
- Issue
- 9
- Pages
- 729-734
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2060157525
- Cited by
- 1,322
- References
- 94
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 31 · 2023: 46 · 2022: 38 · 2021: 33 · 2020: 51 · 2019: 52 · 2018: 60 · 2017: 62 · 2016: 79 · 2015: 87 · 2014: 80 · 2013: 102 · 2012: 98
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pew Charitable Trusts
- Rita Allen Foundation
- Allen Foundation
- National Trust for Historic Preservation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
- Keywords
- mTOR, mTOR inhibitors, mTORC1, mTORC2, cancer therapy, mechanism of action, rapamycin, kinase signaling, targeted cancer drugs
- MeSH terms
- Antineoplastic Agents, Humans, Neoplasms, Protein Kinases, Signal Transduction, Protein Kinase Inhibitors, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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