The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Dissecting the role of mTOR: Lessons from mTOR inhibitors
Open accessAbstract
Recent years have observed significant advances in our understanding of how the serine/threonine kinase target of rapamycin (TOR) controls key cellular processes such as cell survival, growth and proliferation. Consistent with its role in cell proliferation, the mTOR pathway is frequently hyperactivated in a number of human malignancies and is thus considered to be an attractive target for anti-cancer therapy. Rapamycin and its analogs (rapalogs) function as allosteric inhibitors of mTORC1 and are currently used in the treatment of advanced renal cell carcinoma. Rapamycin and its derivatives bind to the small immunophilin FKBP12 to inhibit mTORC1 signalling through a poorly understood mechanism. Rapamycin/FKBP12 efficiently inhibit some, but not all, functions of mTOR and hence much interest has been placed in the development of drugs that target the kinase activity of mTOR directly. Several novel active-site inhibitors of mTOR, which inhibit both mTORC1 and mTORC2, were developed in the last year. In this manuscript, we provide a brief outline of our current understanding of the mTOR signalling pathway and review the molecular underpinnings of the action of rapamycin and novel active-site mTOR inhibitors as well as potential advantages and caveats associated with the use of these drugs in the treatment of cancer.
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Cites
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
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Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
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ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery
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Cited by
Hsu, P. P., Kang, S. A., Rameseder, J., Zhang, Y., Ottina, K. A., Lim, D., Peterson, T. R., Choi, Y., Gray, N. S., Yaffe, M. B., et al. (2011) · Science · doi:10.1126/science.1199498 · Cited by 1,084
Panwar, V., Singh, A., Bhatt, M., Tonk, R. K., Azizov, S., Raza, A. S., Sengupta, S., Kumar, D., & Garg, M. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01608-z · Cited by 967
The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers
Paplomata, E., & O’Regan, R. (2014) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834014530023 · Cited by 593
Properties of FDA-approved small molecule protein kinase inhibitors
Roskoski, R. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.03.006 · Cited by 554
Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors
LoRusso, P. M. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.0018 · Cited by 470
Metadata
- Authors
- Dowling, R. J. O., Topisirovic, I., Fonseca, B. D., & Sonenberg, N.
- Venue
- Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 1804
- Issue
- 3
- Pages
- 433-439
- ISSN
- 1570-9639 (ISSN-L)
- OpenAlex
- W2080127092
- Cited by
- 454
- References
- 14
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- green
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