Lung cancer is the most common source of cancer-related death in the U.S. and worldwide. Lung cancer is a heterogeneous disease, with multiple subtypes characterized by different genetic and molecular profiles, and different response to treatment. One subset of lung cancer is caused by the loss of a gene called LKB1, and approximately 50,000 people are diagnosed with this type of lung cancer in the U.S. each year. Currently, no available therapies elicit sustained clinical benefit for patients with LKB1-mutant lung cancer, and the current overall survival time for such patients from the time of diagnosis is less than one year. Thus, there is great unmet need to rapidly discover and translate clinical options to help these patients. Our recent work has discovered a mechanism of therapeutic resistance (an explanation why tumors do not respond to therapy) that is specific to LKB1-mutant lung tumors. We discovered that two available, clinically-tolerated drugs together can overcome this mechanism, and we are working toward clinical translation of this finding. However, we predict that this finding is only the tip of the iceberg, and that we are poised to discover additional promising therapy approaches as well. Therefore, it is now imperative to fully characterize the mechanisms of therapeutic resistance in this tumor type, as we will do in this project, to expand our understanding of how to treat patients with this disease. The hope is that this study will pave the way toward improved therapeutic options for patients with lung cancer.
Location: Robert H. Lurie Comprehensive Cancer Center - Chicago
Proposal: Elucidating LKB1-specific vulnerabilities in therapeutic resistance in lung cancer