Dr. Flaherty has been the principal investigator of the first combination targeted therapy trial to build on single agent BRAF inhibition in which a selective MEK inhibitor is combined with this agent. In addition to being the academic architect of these clinical trial protocols, Dr. Flaherty and colleagues at DF/HCC have accrued the largest number of patients to these trials. As a consequence, our center not only has the longest clinical experience with these agents, but also an increasingly large repository of archival tumor specimens and fresh tumor biopsies obtained before and during treatment, as well as at the time of clinical progression. This Core will continue to collect tumor biopsies prior to and during treatment with BRAF inhibitors, and then identify and isolate cellular constituents of the tumor microenvironment including immune subpopulations, endothelial cells, pericytes, and fibroblasts. We will also genetically characterize tumor cells for previously described oncogene and tumor suppressor gene alterations including point mutations and copy number. Our group is uniquely poised to direct our clinical and research infrastructure to studying the problem of resistance to BRAF targeted therapy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1-SRLB-3)
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University of Texas MD Anderson Cancer Center
United States
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Wargo, Jennifer A; Cooper, Zachary A; Flaherty, Keith T (2014) Universes collide: combining immunotherapy with targeted therapy for cancer. Cancer Discov 4:1377-86
Smith, Michael P; Sanchez-Laorden, Berta; O'Brien, Kate et al. (2014) The immune microenvironment confers resistance to MAPK pathway inhibitors through macrophage-derived TNF?. Cancer Discov 4:1214-29
Cooper, Zachary A; Juneja, Vikram R; Sage, Peter T et al. (2014) Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol Res 2:643-54
Shi, Min; Roemer, Margaretha G M; Chapuy, Bjoern et al. (2014) Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain. Am J Surg Pathol 38:1715-23
Sullivan, Ryan J; Lorusso, Patricia M; Flaherty, Keith T (2013) The intersection of immune-directed and molecularly targeted therapy in advanced melanoma: where we have been, are, and will be. Clin Cancer Res 19:5283-91
Frederick, Dennie T; Piris, Adriano; Cogdill, Alexandria P et al. (2013) BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res 19:1225-31
Chen, Benjamin J; Chapuy, Bjoern; Ouyang, Jing et al. (2013) PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res 19:3462-73