5-alpha reductase inhibitor use and risk of lung cancer

5-alpha reductase inhibitor use and risk of lung cancer

Funding for this project has been requested from the Manitoba Health Research Council.

Researcher/analysis time is provided as in-kind contributions from the affiliated institutions.

None

Lung cancer is the leading cause of cancer-related mortality worldwide. The majority of patients present with advanced, non-curable disease, with an expected median overall survival of approximately 9 months. Molecularly targeted agents for lung cancer have only modest benefit in selected groups of patients and are limited by their considerable cost. We seek to evaluate the role of androgen pathway modification in lung cancer as a novel targeted approach to prevention and treatment in this devastating disease.

Males with lung cancer have poorer outcomes compared to females, however, the mechanism of this phenomenon remains unknown. This difference may be, in part, mediated by exposure to sex hormones (estrogens and androgens). Expression of the androgen receptor has been demonstrated in some lung cancers, and in vitro studies demonstrate a response to androgen agonists and antagonists with corresponding changes in transcription of genes responsible for survival, oxygen utilization, DNA repair and apoptosis. Our population-based data has demonstrated an association between exposure to androgen pathway modification and improved survival in males with non-small cell lung cancer (NSCLC). We hypothesize that androgens play a significant role in the pathogenesis of a subgroup of NSCLC and that the use of androgen pathway modification will improve outcome in this group.

Androgen deprivation therapies are well established in the targeted treatment of prostate cancer. The considerable long-term clinical safety and efficacy data of these agents and their low cost make them attractive for study in diseases that may be mediated by androgens, such as lung cancer. Further data on patient outcome in those taking these drugs is needed to translate these preliminary findings into a randomized clinical trial.

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