Seyed Javad Moghaddam, M.D.

Mutations of KRAS gene are the most common genetic alterations found in lung cancer. These mutations are heavily associated with tobacco exposure, and poor prognosis. Unfortunately, our knowledge of the molecular mechanisms affecting KRAS-induced lung cancer growth is deficient. Moreover, attempts at targeting KRAS mutant lung tumors with drugs have thus far failed, clearly indicating that alternative strategies are needed. Our goals are to understand gender- and cell-specific signaling pathways that are involved in KRAS mutant lung cancer growth, and to target these pathways and ultimately develop personalized therapies for this fatal subtype of lung cancer.

Update: We found that the deletion of a gene and its respective protein called STAT3 in cells lining the airways resulted in a significant reduction of KRAS mutant tumors in female mice, whereas it caused a dramatic increase in tumor growth in male mice. We also found depletion of a particular type of white blood cells called neutrophils in male mice resulted in reduced lung tumor growth, while inhibiting estrogen (sex hormone) receptor signaling in female mice led to the development of lung tumors. These findings suggest a dynamic interplay between estrogen signaling and KRAS/STAT3 pathways in lung cancer development.