Molecular mechanisms of smoking-associated lung cancer
Initial Award Abstract
Lung cancer is the leading cause of cancer death and the second most common cancer among both men and women in the United States. About a fifth of lung cancer cases are missing an anti-cancer gene called LKB1. Cancers missing LKB1 are often aggressive, rapidly spreading through the body.
In our laboratory, we have observed that loss of the LKB1 gene leads to activation of a protein called CREB in the lungs. CREB plays a vital role in the brain in the process of addiction to tobacco and in the development of different types of cancers. However, the role of CREB in lung cancer remains unknown. Importantly, smoking tobacco has been shown to cause mutations in LKB1 and activation of CREB in the lungs. These observations suggest that tobacco may be activating CREB in the brain to promote addiction, and also in the lungs, by inducing mutations in LKB1, to promote tumor formation.
In this project, we will study the role of CREB as a mediator of tobacco-related lung cancer. Finding out how tobacco via CREB promotes lung cancer will help us to understand tobacco-related disease and will set the basis for better identification and treatment of patients with lung cancer. Drugs targeting CREB are being developed and could be used as effective anti-cancer agents and to prevent tobacco addiction.