Cited by 429PI3K/AKT/mTOR signaling in cancerAdvanced Breast Cancer TherapiesMetabolism, Diabetes, and Cancer

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Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

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Wander, Seth A., Hennessy, Bryan T., Slingerland, Joyce M.·2011·Journal of Clinical Investigation

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Abstract

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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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.
ORCID: Wander, Seth A.
Hennessy, Bryan T.
Slingerland, Joyce M.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2011-04-01
Volume: 121
Issue: 4
Pages: 1231-1241
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci44145
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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Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

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