The DOI matches its Crossref record; 156 of the 157 references it cites were found in a registry or an index.
Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy
Open accessAbstract
Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.
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“our findings indicate that by preserving the tissue repopulating capacity of the epithelial stem cells, mTOR inhibition with rapamycin and newly developed agents (Wander et al., 2011) may prevent the appearance of radiation-induced mucositis and its consequent negative impact on anticancer treatment outcome and cost”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Wander et al., 2011
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“Treatments targeting key components of tumor hypoxia signaling pathways, including mTOR, are one of the current approaches to cancer therapy.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [182]
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Cited by
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mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
MTOR: a pharmacologic target for autophagy regulation
Kim, Y. C., & Guan, K.-L. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73939 · Cited by 2,126
PI3K and cancer: lessons, challenges and opportunities
Fruman, D. A., & Rommel, C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4204 · Cited by 1,762
Rapamycin: one drug, many effects
Li, J., Kim, S. G., & Blenis, J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.001 · Cited by 1,287
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134
Metadata
- Authors
- Wander, S. A., Hennessy, B. T., & Slingerland, J. M.
- Affiliations
- University of Miami (US)
- Royal College of Surgeons in Ireland (IE)
- Corresponding author
- Slingerland, Joyce M.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-04-01
- Volume
- 121
- Issue
- 4
- Pages
- 1231-1241
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3069769
- OpenAlex
- W2025935112
- Cited by
- 427
- References
- 157
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 10 · 2023: 18 · 2022: 16 · 2021: 14 · 2020: 23 · 2019: 23 · 2018: 27 · 2017: 39 · 2016: 28 · 2015: 63 · 2014: 51 · 2013: 47 · 2012: 28
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Doris Duke Charitable Foundation
- National Institutes of Health (5-R01-)
- National Cancer Institute (5-R01-CA-105118-04, R01CA105118)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Oncology › Advanced Breast Cancer Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTOR inhibitors, mTOR signaling, mTORC1, mTORC2, PI3K-related kinases, cancer therapy, therapeutic target
- MeSH terms
- Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Phosphoinositide-3 Kinase Inhibitors, Antineoplastic Agents, Clinical Trials as Topic, Female, Humans, Male, Neoplasms, Transcription Factors, Signal Transduction, Phosphatidylinositol 3-Kinases, Sirolimus, Tumor Suppressor Proteins, Protein Kinase Inhibitors, TOR Serine-Threonine Kinases
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