Integrating clinical, functional and chemical genomics to understand lung cancer biology
Lung cancer is the leading cause of cancer mortality worldwide. Contributing factors include the late stage of disease at the time of diagnosis and a scarcity of effective therapeutic strategies to treat advanced tumors. However, as our knowledge of lung cancer biology is increasing, targeted therapies have been developed to combat this devastating disease. These therapies target mutated components of key cellular pathways on which tumors have become dependent on for survival, yielding drastic initial response rates without the major side effects of traditional chemotherapies.
Despite these successes, two major problems remain: first, the majority of lung cancer patients have tumors without mutations in targetable genes and; second, patients eventually develop resistance to treatment with these targeted agents. In addition, since lung tumors commonly have hundreds of mutated genes, it is difficult to pinpoint those that are responsible for tumor growth and resistance to therapy, creating a clear bottleneck in the translation of laboratory findings to a clinical setting.
Through analysis of the genomic profiles of human lung tumors, Dr. Lockwood’s research program aims to identify novel genes and pathways that are altered during lung cancer development. Furthermore, by combining this information with the characterization of mice genetically engineered to develop lung tumors, he will attempt to elucidate the key genes driving lung cancer initiation, progression and response to therapy. Lastly, by screening libraries of chemical compounds across lung cancer cells, Dr. Lockwood aims to characterize novel inhibitors of these identified genes and their corresponding pathways that show promise for use as targeted therapies.
Together, this work will further understanding of lung cancer biology and create insight toward the development of new approaches to diagnose and treat patients suffering from this disease.