The AACR-AstraZeneca-Prevent Cancer Foundation Fellowship for Translational Lung Cancer Research is open to postdoctoral fellows and clinical research fellows at an academic facility, teaching hospital or research institution who will be in the first, second or third year of their postdoctoral training at the start of the grant term. Proposed research projects must relate directly to translational lung cancer research.
2008 GRANTEE
Lauren A. Byers, M.D. Hematology-Oncology Medical Fellow, UT MD Anderson Cancer Center, Houston, TX
Validation of a Proteomic Signature of Pemetrexed Resistance in NSCLC
"In non-small cell lung cancer (NSCLC), disease progression and therapeutic resistance can be driven by a variety of signaling pathways. Because of this, lung cancer patients vary greatly in their response to chemotherapies and targeted agents. We hypothesize that this molecular heterogeneity will be reflected in a tumor's proteomic signature prior to treatment, and that this signature can be used to predict sensitivity or resistance to a given drug. Using reverse-phase protein arrays (RPPA), a high throughput antibody-based technology, we previously compared proteins and phosphoproteins from key signaling pathways between pemetrexed-sensitive and -resistant NSCLC cell lines and derived a proteomic signature of pemetrexed resistance. We also identified several key signaling molecules associated with pemetrexed resistance that are potential therapeutic targets. In this project, we will validate this newly developed "pemetrexed response signature" in vitro and in vivo and test therapeutic targets included within the signature for their ability to abrogate pemetrexed resistance. Ultimately, we hope to translate these results into a clinical tool for predicting response to pemetrexed and to identify new biologically-based, rational drug combinations with pemetrexed. In the future, we plan to use this project as a model for testing our other drug-response signatures in NSCLC. Receiving the AACR-AstraZeneca-Prevent Cancer Foundation Fellowship for Translational Lung Cancer Research is a true honor. This award provides not only significant support for this project, but will also help me grow further as a translational researcher. I am also extremely grateful to my past mentors, Drs. Arnold Levine, Louis Staudt and Louise Strong, and to my current mentors, Drs. John Heymach and Waun Ki Hong, who have been incredible role models and have shaped my development as a physician-scientist."
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