Dr. David Brian Shackelford, Assistant Professor of Medicine at the David Geffen School of Medicine at the University of California, Los Angeles, has been awarded the first Momentum Research Award for his research “Targeting cancer metabolism in therapy-resistant EGFR-mutant lung cancer.” The Momentum Research Award: Defeating Lung Cancer in Women is a two-year, $250,000 award designed to fund an innovative and transformational proposal that shows potential for high impact in diagnosing and treating lung cancer in women, and is the first joint collaborative research award between the Bonnie J. Addario Lung Cancer Foundation (ALCF) and the American Lung Association (ALA).
Under the Momentum Research Award grant, Dr. Shackelford will work to understand the link between cell metabolism and cancer initiation, progression and resistance to therapy, focusing on cancer metabolism in therapy-resistant EGFR mutant lung cancer. Women are much more likely to experience treatment resistant EGFR-mutation positive non-small cell lung cancer (NSCLC) and it is Dr. Shackelford’s goal to understand this association, and identify ways to overcome treatment resistance – first in preclinical animal models and eventually through a clinical trial. Dr. Shackelford’s approach represents a new approach for the treatment of lung cancer in women by developing personalized therapeutic strategies that selectively target metabolic needs to overcome therapy resistance.
Dr. Shackelford and his team have identified that EGFR-mutant lung cancer utilizes both glucose and glutamine to support its growth and proliferation. They aim to specifically inhibit this dependence of the cancer cells using a combination of two approaches: 1) they will use PET (positron emission tomography) imaging, with the agents 18F- fluoro-2-deoxyglucose (18F-FDG) and 11C-Glutamine (11C-Gln), to non-invasively profile glucose and glutamine metabolism in erlotinib-resistant EGFR-mutant lung tumors, and 2) the team is also evaluating combinations of targeted therapies that inhibit both the utilization of glucose (glycolysis) and glutamine (glutaminolysis). Combining these two approaches- the PET imaging will guide the delivery of targeted therapies- will allow them to overcome treatment-resistance in EGFR-mutant lung cancer. In effect, through this approach, Dr. Shackelford aims to simultaneously starve cancer cells of both glucose and glutamine, thereby blocking cancer cell proliferation. Dr. Shackelford and his team will also identify predictive biomarkers of response, and validate their utility in animal models.