AB 43. The corticotropin releasing factor system in lung cancer: expression and pathophysiol ogical implications

Abstract: Lung cancers express multiple factors that hold some role in the regulating networks supporting their ectopic growth. Recently, increased interest is developing in the expression and biological role of the neuropeptides and receptors of the Corticotropin Releasing Factor (CRF) system, the principle neuroendocrine mediator of the stress response, especially in the light of several R&D programs for small molecule antagonists that could present some anticancer therapeutic benefit. In the present article we review the literature suggesting that the CRF system could be involved in the regulation of lung cancer genesis and progression. Results demonstrated expression of immunoreactive CRF in a small percentage of lung cancer tissues. The presence of functional CRF receptors was also demonstrated in small cell lung carcinoma cell lines but not in the respective tissue biopsies, reducing the pathophysiological relevance of the former findings. Finally, in a mouse cachexia model, administration of a CRF2 agonist resulted in beneficial effects on muscle weight loss in mice with implanted fastgrowing Lewis lung carcinoma, and reduced both the number of metastases and their mass. These results could be clinically exploited by presenting targets of new therapeutic approaches.

Funding: This research has been co-financed by the European Union (European social fund - ESF) and Greek national funds through the operational program “education and lifelong learning” of the National Strategic Reference Framework (NSRF) - research funding program: heracleitus II. Investing in knowledge society through the European social fund.