2010 UALC
James DeGregori, PhD
University of Colorado Denver Anschutz Medical Campus
Research Project:
Manipulating cytokine-dependent signaling to sensitize NSCLC cells to EGFR inhibition
Summary:
Dr. DeGregori is seeking ways to overcome resistance to EGFR-targeted therapies. Using a screen, Dr. DeGregori and his team identified a number of other targets that could be inhibited to increase responsiveness to EGFR-targeted therapies. Many of these targets already have FDA-approved drugs; Dr. DeGregori and his team will use different combinations of these drugs in both cell lines and mouse models to improve responsiveness to EGFR-therapies. This work will provide critical information for future combination trials in lung cancer patients.
More Content:
Final Report
Dr. DeGregori’s team identified that the canonical Wnt pathway and tankyrase in particular contribute to resistance of non-small cell lung cancer (NSCLC) cells to EGFR-targeted therapies. These studies reveal a potential mechanism underlying synergistic NSCLC cell killing from combined inhibition of EGFR and tankyrase. Dr. DeGregori is in discussions with a pharmaceutical company about support for a Phase I clinical trial to test combinations of EGFR inhibitors with a tankyrase inhibitor in lung cancer patients. They will continue to dissect the role of the Wnt, tankyrase, CK2 and Jak2 pathways in NSCLC survival during EGFR inhibition, with the goal of developing therapeutic strategies. They are currently putting significant effort into pre-clinical models. Depending on the results, Dr. DeGregori’s team hopes to transition discoveries into clinical trials within 3 years.
Notable Accomplishments
Before obtaining funding from UALC, Dr. DeGregori’s lab was entirely focused on leukemia research. Stimulated by the results from this grant, half of the lab now work on lung cancer, and the lab is well funded to continue research in this field. Supported by work funded by UALC, Dr. Gregori and his colleagues at UC Denver have garnered over $2 million in follow-on funding. Dr. DeGregori has published his work in Cancer Research.