The IKBKE gene, one of a family of complex enzymes involved in increasing cellular inflammation. overexpression of IKBKE has been linked to the development of breast and prostate cancers. However, until then, it has not been linked to environmental carcinogens such as tobacco smoke. Tobacco smoke, has been documented to be the most potent initiator and promoter of lung cancer. The traditional model suggests that the components of tobacco promote cancer development through a process that causes DNA damage. Recent studies have shown that tobacco smoke can also promote lung cancer by altering the proliferation and survival pathways of regulatory cells. This study, in an effort to find potential drug targets for the treatment of non-small cell lung cancer, explored the identification and understanding of one of these signaling channels. In this study, IKBKE was found to induce cancer through two tobacco carcinogens: nicotine, found in tobacco smoke, and a nicotine-derived nitrosamines. Their findings suggest that IKBKE is a key molecule associated with tobacco-induced lung cancer. Jin Q. Cheng, a senior member of Moffitt’s Department of Molecular Oncology and first author of the paper, explained, “Because the IKBKE kinase is produced induced by tobacco, a small molecule inhibitor of IKBKE may be a drug with therapeutic potential for tumors. Current treatments for non-small cell lung cancer include surgery, radiation therapy and chemotherapy. However, patients eventually become tolerant to treatment. The authors believe that a better understanding of the molecular mechanisms of tolerance, and the development of new targeted gene therapies that can circumvent tolerance, is essential. In this study, the researchers also report for the first time that IKBKE is a target of STAT3, a transcription factor that plays a key role in many cellular life processes such as cell growth and apoptosis According to the researchers, STAT3 is often activated in different types of cancer in humans, and when STAT3 is activated, it enhances the overexpression of IKBKE and increases the levels of this protein. In non-small cell lung cancer, the induction of IKBKE by nicotine depends on the role of STAT3. The authors noted that the activation phase of STAT3 implies the existence of an attractive therapeutic potential, since IKBKE is a target of STAT3. When IKBKE induces chemoresistance, such as when IKBKE expression is blocked, cancer cells become sensitive to chemotherapy and have reduced survival. Cheng concluded, “Because overexpression of IKBKE kinase is induced by tobacco smoke, and because IKBKE levels are elevated in response to nicotine and nicotine-derived nitrosamides, this aspect of the evidence could potentially be applied to intervention strategies for non-small cell lung cancer to develop drugs that target IKBKE. This research was supported by National Cancer Institute grants CA137041 and P50CA119997, and the James and Esther? King Biomedical Research Program grants 1KG02, 1KD04, and 1KN08. About Moffitt Cancer Center Moffitt, located in Tampa, is one of only 41 comprehensive cancer centers designated by the National Cancer Institute and recognizes Moffitt as a center of excellence for its contributions to research, clinical trials and cancer prevention and control. Since 1999, it has been ranked by U.S. News & World Report as one of the “Best Hospitals in America” for the treatment of cancer. Moffitt employs more than 4,200 people and has a national economic impact of nearly $2 billion. For more information, visit MOFFITT.org and follow Moffitt on Facebiik, twitter and YouTube.