Meet our grantees: Dr. Darren Tyson, Vanderbilt University Medical Center
Variability of erlotinib response in lung cancer.
Over the past decade, we have learned that lung and other cancers are caused by specific ‘driver’ mutations that cause cancer cells to grow uncontrollably. By targeting these malfunctioning genes with specific drugs, we can achieve more effective treatments for patients than traditional chemotherapy alone. Patients whose tumors have known driver mutations generally respond well to targeted therapies, such as the FDA-approved erlotinib (targeting EGFR) and crizotinib (targeting ALK).
However, the durability of response is highly variable from patient to patient. For example, the majority of patients with EGFR-positive lung cancers respond to treatment with erlotinib. Yet, patient responses can vary from a small number of non-responders whose tumors continue to grow during treatment to responders who show decreases in tumor size anywhere from approximately 15% to 95%.
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. will be employing an innovative 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.
In Aim 1, Dr. Tyson will assess variability within and between cell lines by measuring response rates of individual colonies. In Aim 2, four different sublines will be grown in vivo to explore whether variability seen in vitro predicts in vivo response. This project will provide proof-of-principle for clinical studies, and at the same time make it possible to work out the technical details and/or unforeseen obstacles to move into clinical trials.
Dr. Darren Tyson is a Research Assistant Professor in the Department of Cancer Biology at Vanderbilt University in Nashville, Tennessee. Dr. Tyson’s grant is co-sponsored by The Hank Thompson Fund, Lily's Light, and Caine Halter Fund for Lung Cancer Research.