The Role of the Akt/mTOR Pathway in Tobacco Carcinogen–Induced Lung Tumorigenesis

Lung cancer is the leading cause of cancer-related death in the United States, and 85 to 90% of lung cancer cases are associated with tobacco use. Tobacco components promote lung tumorigenesis through genotoxic effects, as well as through biochemical modulation of signaling pathways such as the Akt/...

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Bibliographic Details
Published in:Clinical cancer research 2010-01, Vol.16 (1), p.4-10
Main Authors: MEMMOTT, Regan M, DENNIS, Phillip A
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Carcinogens - toxicity
Humans
Indoles - therapeutic use
Inositol - therapeutic use
Intracellular Signaling Peptides and Proteins - antagonists & inhibitors
Intracellular Signaling Peptides and Proteins - physiology
Lung Neoplasms - chemically induced
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Medical sciences
Mice
Nicotiana - toxicity
Pharmacology. Drug treatments
Protein Serine-Threonine Kinases - antagonists & inhibitors
Protein Serine-Threonine Kinases - physiology
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - metabolism
Rotenone - analogs & derivatives
Rotenone - therapeutic use
Signal Transduction - drug effects
Sirolimus - therapeutic use
Smoking
Tobacco, tobacco smoking
TOR Serine-Threonine Kinases
Toxicology
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Summary:Lung cancer is the leading cause of cancer-related death in the United States, and 85 to 90% of lung cancer cases are associated with tobacco use. Tobacco components promote lung tumorigenesis through genotoxic effects, as well as through biochemical modulation of signaling pathways such as the Akt/mammalian target of rapamycin (mTOR) pathway that regulates cell proliferation and survival. This review will describe cell surface receptors and other upstream components required for tobacco carcinogen–induced activation of Akt and mTOR. Preclinical studies show that inhibitors of the Akt/mTOR pathway inhibit tumor formation in mouse models of carcinogen-induced lung tumorigenesis. Some of these inhibitors will be highlighted, and their clinical potential for the treatment and prevention of lung cancer will be discussed. Clin Cancer Res; 16(1); 4–10
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-09-0234