Research


In the laboratory we study lung cancer to answer the following questions: What are the alterations in cellular pathways that cause tumors to form? How can we interfere with these pathways to get tumors to regress? How do tumors become resistant to drugs? How can we detect tumors early when they are still curable?

Not all lung cancers are the same. There are two major histopathological categories of lung cancer: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer is the most common accounting for 80% of all lung cancers. NSCLC itself can be divided into three histological subtypes: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Lung adenocarcinomas are the most frequent and the genetics of these tumors has been studied extensively in recent years. In the lab we focus on one of the genes that is mutated in lung adenocarcinomas-the Epidermal Growth Factor Receptor (EGFR) gene

alt text

Mutations in the Epidermal Growth Factor Receptor (EGFR) gene are found in 10-20% of lung adenocarcinomas. These mutations are most common in tumors in never-smokers and are associated with sensitivity to drugs that specifically block the activity of the mutant receptor. Patients with EGFR mutant tumors initially respond to treatment with these drugs, however drug-resistant disease almost invariably emerges within a year of starting treatment. In our laboratory we study: 1) how the mutant receptors alter signaling pathways in lung cells to cause cancer and, 2) mechanisms of resistance to therapies directed against mutant EGFR.
alt text

alt text

The main approach employed by our laboratory is to use genetically engineered mouse models of the human disease. Several years ago, we generated mice that express mutant EGFR in the lung. The mice develop lung adenocarcinomas that are sensitive to treatment with tyrosine kinase inhibitors. However, even mice develop drug-resistant disease. These tools combined with approaches in cell culture and by analyzing human specimens are very powerful to help us understand the molecular mechanisms at the heart of lung adenocarcinoma development.

alt text

alt text