Journal
LUNG CANCER
Volume 72, Issue 2, Pages 154-159Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2011.01.019
Keywords
Lung cancer; Synergistic drug interactions; Tumor microenvironment; TZDs; PPAR-gamma ligands; TGF-beta
Categories
Funding
- NIH/NCI [CA132571-01]
- American Cancer Society [RSG-CSM-116801]
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Peroxisome proliferator-activated receptors (PPAR)-gamma belongs to the nuclear hormone receptor superfamily of ligand-dependent transcription factors. It is a mediator of adipocyte differentiation, regulates lipid metabolism and macrophage function. The ligands of PPAR-gamma have long been in the clinic for the treatment of type II diabetes and have a very low toxicity profile. Activation of PPAR-gamma was shown to modulate various hallmarks of cancer through its pleiotropic affects on multiple different cell types in the tumor microenvironment. An overwhelming number of preclinical-studies demonstrate the efficacy of PPAR-gamma ligands in the control of tumor progression through their affects on various cellular processes, including cell proliferation, apoptosis, angiogenesis, inflammation and metastasis. A variety of signaling pathways have been implicated as potential mechanisms of action. This review will focus on the molecular basis of these mechanisms; primarily PPAR-gamma cross-regulation with other signaling pathways and its relevance to lung cancer therapy will be discussed. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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