The DOI matches its Crossref record; 231 of the 256 references it cites were found in a registry or an index.
Rapamycin: An anti-cancer immunosuppressant?
Abstract
Rapamycin and its derivatives are promising therapeutic agents with both immunosuppressant and anti-tumor properties. These rapamycin actions are mediated through the specific inhibition of the mTOR protein kinase. mTOR serves as part of an evolutionarily conserved signaling pathway that controls the cell cycle in response to changing nutrient levels. The mTOR signaling network contains a number of tumor suppressor genes including PTEN, LKB1, TSC1, and TSC2, and a number of proto-oncogenes including PI3K, Akt, and eIF4E, and mTOR signaling is constitutively activated in many tumor types. These observations point to mTOR as an ideal target for anti-cancer agents and suggest that rapamycin is such an agent. In fact, early preclinical and clinical studies indicate that rapamycin derivatives have efficacy as anti-tumor agents both alone, and when combined with other modes of therapy. Rapamycin appears to inhibit tumor growth by halting tumor cell proliferation, inducing tumor cell apoptosis, and suppressing tumor angiogenesis. Rapamycin immunosuppressant actions result from the inhibition of T and B cell proliferation through the same mechanisms that rapamycin blocks cancer cell proliferation. Therefore, one might think that rapamycin-induced immunosuppression would be detrimental to the use of rapamycin as an anti-cancer agent. To the contrary, rapamycin decreases the frequency of tumor formation that occurs in organ transplant experiments when combined with the widely used immunosuppressant cyclosporine compared with the tumor incidence observed when cyclosporine is used alone. The available evidence indicates that with respect to tumor growth, rapamycin anti-cancer activities are dominant over rapamycin immunosuppressant effects.
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“Sirolimus, which is an mTOR inhibitor, possesses antitumor activity 171”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [171]
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1 retracted
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TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
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Research works printed but not linked: 1
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LKB1-Dependent Signaling Pathways
Alessi, D. R., Sakamoto, K., & Bayascas, J. R. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142702 · Cited by 805
Rapamycin causes regression of astrocytomas in tuberous sclerosis complex
Franz, D. N., Leonard, J. M., Tudor, C., Chuck, G., Caré, M. M., Sethuraman, G., Dinopoulos, A., Thomas, G., & Crone, K. R. (2006) · Annals of Neurology · doi:10.1002/ana.20784 · Cited by 609
A Review of the Microbial Production of Bioactive Natural Products and Biologics
Pham, J. V., Yilma, M. A., Feliz, A., Majid, M. T., Maffetone, N., Walker, J. R., Kim, E., Cho, H. J., Reynolds, J. M., Song, M., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01404 · Cited by 570
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Cancer in the Transplant RecipientPreprint
Chapman, J. R., Webster, A. C., & Wong, G. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a015677 · Cited by 277
Metadata
- Authors
- Law, B. K.
- Affiliations
- University of Florida (US)
- Corresponding author
- Law, Brian K.
- ORCID
- Law, Brian K.
- Venue
- Critical Reviews in Oncology/Hematology
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 56
- Issue
- 1
- Pages
- 47-60
- ISSN
- 1040-8428 (ISSN-L)
- OpenAlex
- W2764507256
- Cited by
- 252
- References
- 256
- Citations by year
- 2026: 1 · 2025: 12 · 2024: 14 · 2023: 16 · 2022: 14 · 2021: 9 · 2020: 8 · 2019: 18 · 2018: 9 · 2017: 15 · 2016: 9 · 2015: 10 · 2014: 23 · 2013: 16 · 2012: 10
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Critical Reviews in Oncology/Hematology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- rapamycin, mTOR signaling, immunosuppression, anticancer activity, tumor angiogenesis, apoptosis, tumor cell proliferation, cyclosporine, organ transplantation, tumor suppression, PI3K/Akt signaling, TSC1/TSC2, PTEN, LKB1, eIF4E
- MeSH terms
- Animals, Antineoplastic Agents, Cell Cycle, Drug Synergism, Humans, Immunosuppressive Agents, Neoplasms, Neovascularization, Pathologic, Protein Kinases, Drug Design, Signal Transduction, Molecular Chaperones, Sirolimus, TOR Serine-Threonine Kinases
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