Lung Cancer

Lung cancers (LCs) have been defined as a major disease of the aged with disappointing survival statistics and represent the second most common type of cancer in both genders worldwide [90]. Another major inducer of LCs is cigarette smoking, although specific LC subtypes do not correlate with either age or smoking status (i.e. lung adenocarcinoma is more characteristic of young females) [91]. Cigarette smoke has also been shown to decrease PPARy expression in the lungs leading to detrimental effects suggesting that PPARy agonist treatment may counteract negative effects related to smoking and ageing. Indeed it was shown that treatment targeting PPARy can significantly inhibit cigarette smoke-induced mucin production [92]. It has also been reported that exposure to acrolein, one of the most toxic compounds found in cigarette smoke, induces goblet cell hyperplasia in bronchial epithelium and induces airway inflammation, as shown by the increased levels of inflammatory cytokines including IL-1p, IL-8, and TNF-a in bronchial fluid. Treatment with TGZ before acrolein exposure was reported to alleviate these changes in a dose-dependent manner providing evidence for PPARy efficiency in counteracting smoking [75]. These studies suggest a role of PPARy in lung tumorigenesis, and suggest PPARs as potential biomarkers of lung tumours. Furthermore, the enhancement of PPARy activity (through i.e. TZDs) could prevent the formation of lung cancer, or serve as adjuvant during lung cancer therapy. However, once tumour cells have been formed the situation may change. It has been reported that systemic administration of TGZ accelerates tumour metastasis in models of non-small cell lung cancer [93] and does not provide any survival benefit. Therefore systemic administration of PPARy agonists should be avoided in advanced lung cancer, but again local administration perhaps via inhalers may reach the desired effect.

 
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