Funded Research

Novel druggable pathway required for lung cancer progression and metastasis

fr1Ann Marie Pendergast, PhD
Duke University Medical Center

Sponsored by The Hank Thompson Fund and Lily’s Light and The Caine Halter Fund for Lung Cancer Research
Funded 2013

Summary
Dr. Pendergast will investigate targeting the two Abl family kinases, Abl and Arg, in lung adenocarcinoma. Her team identified a role for Abl kinases in the progression and metastasis of some NSCLC tumors, characterized by poor prognosis and few therapeutic options. In addition, new data predicts Abl kinases to be involved in over 15% of lung tumors. Dr. Pendergast’s team will investigate the role of Abl kinases in lung adenocarcinoma tumor progression and metastasis, and test whether inhibiting Abl kinases can resensitize drug-resistance tumors to treatment.

 

Variability of erlotinib response in lung cancer

fr2Darren Tyson, PhD
Vanderbilt University Medical Center

Sponsored by The Hank Thompson Fund and Lily’s Light and the Caine Halter Fund for Lung Cancer Research
Funded 2012

Summary
Patients whose tumors have known driver mutations generally respond well to targeted therapies, such as erlotinib or crizotinib, although the durability of response is highly variable from patient to patient. Knowing in advance which tumors will progress most rapidly would indicate which patients should be treated more aggressively. Currently there is no way to predict tumor response, necessitating a “wait and see” approach. Dr. Tyson will be using a novel method to characterize this variability in response to erlotinib, using a novel assay and a predictive model. If successful, this work could have significant impact on how patients are treated, enabling doctors to predict which patients will or will not respond to current and future targeted therapies.

 

Manipulating cytokine-dependent signaling to sensitize NSCLC cells to EGFR inhibition

fr3James DeGregori, PhD
University of Colorado, Denver

Sponsored by Lily’s Light™ and Joan’s Legacy
Funded 2010

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.

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.