2010 UALC
Paul Paik, MD
Memorial Sloan Kettering Cancer Center
Research Project:
Characterization of the Molecular Heterogeneity of EGFR Mutant Lung Adenocarcinoma: Baseline and Post-Treatment Tumor Analysis
Summary:
Many lung cancer patients who have mutations to the EGFR gene initially respond well to EGFR-targeted therapies; unfortunately, patients can quickly develop resistance to this therapy. However, it remains unclear why some patients may have a more positive response and/or respond to therapy for a longer amount of time. By assessing the state of the tumor before and after treatment with erlotinib, Dr. Paik will uncover genes correlated with clinical outcomes. These genes can then be targeted in the future to help combat resistance to therapy.
More Content:
Final Report
The project has generated two hypotheses that Dr. Paik is planning to test in other models. He has started a new collaboration with Dr. Massagué and Dr. Acharyya to extend their work on the TNF-alpha/CXCL1/2/S100A8 pathway into EGFR mutant lung cancer cell lines and mouse models to determine the role that their paracrine inflammatory loop has on the development of acquired resistance to erlotinib, tumor sensitivity to erlotinib, and evolution of metastases. The second project will involve experiments coupling the anti-PD1 monoclonal antibody BMS-936558 with erlotinib in EGFR mutant cell lines and mouse models to confirm data obtained in this project. Dr. Paik and his team have also started a series of cross-platform validation experiments using immunohistochemistry to study the key pathway genes identified from this study in the remaining tumor samples (S100A8/9, CXCL1/2, PD-L1, among others). Finally, Dr. Paik and his team continue to accrue patients as funding allows to this study to increase the overall sample size.