sirolimus and indole-3-carbinol

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.

Topics: Animals; Carcinogens; Humans; Indoles; Inositol; Intracellular Signaling Peptides and Proteins; Lung Neoplasms; Mice; Nicotiana; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Rotenone; Signal Transduction; Sirolimus; Smoking; TOR Serine-Threonine Kinases