The DOI matches its Crossref record; 93 of the 94 references it cites were found in a registry or an index.
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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In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
Self-citationUpstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083
Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,051
Self-citationSarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665
Self-citationmTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
O'Reilly, K. E., Rojo, F., She, Q.-B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2925 · Cited by 2,561
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365
Self-citationMammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive
Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Rüegg, M. A., Hall, A., & Hall, M. N. (2004) · Nature Cell Biology · doi:10.1038/ncb1183 · Cited by 2,097
Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., & Hall, M. N. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00636-6 · Cited by 1,886
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
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