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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163125-02
Application #
8555328
Study Section
Special Emphasis Panel (ZCA1-SRLB-3 (O1))
Project Start
2011-09-21
Project End
2016-07-31
Budget Start
2012-09-05
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$165,635
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Friedman, Adam A; Xia, Yun; Trippa, Lorenzo et al. (2017) Feasibility of Ultra-High-Throughput Functional Screening of Melanoma Biopsies for Discovery of Novel Cancer Drug Combinations. Clin Cancer Res 23:4680-4692
Roh, Whijae; Chen, Pei-Ling; Reuben, Alexandre et al. (2017) Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci Transl Med 9:
Juneja, Vikram R; McGuire, Kathleen A; Manguso, Robert T et al. (2017) PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med 214:895-904
Kwong, Lawrence N; Zou, Lihua; Chagani, Sharmeen et al. (2017) Modeling Genomic Instability and Selection Pressure in a Mouse Model of Melanoma. Cell Rep 19:1304-1312
Reuben, Alexandre; Spencer, Christine N; Prieto, Peter A et al. (2017) Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma. NPJ Genom Med 2:
Xu, Jie; Sun, Heather H; Fletcher, Christopher D M et al. (2016) Expression of Programmed Cell Death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and Dendritic Cell Disorders. Am J Surg Pathol 40:443-53
Tung, Nadine; Garber, Judy E; Hacker, Michele R et al. (2016) Prevalence and predictors of androgen receptor and programmed death-ligand 1 in BRCA1-associated and sporadic triple-negative breast cancer. NPJ Breast Cancer 2:16002
Smith, Michael P; Brunton, Holly; Rowling, Emily J et al. (2016) Inhibiting Drivers of Non-mutational Drug Tolerance Is a Salvage Strategy for Targeted Melanoma Therapy. Cancer Cell 29:270-84
Chen, Pei-Ling; Roh, Whijae; Reuben, Alexandre et al. (2016) Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade. Cancer Discov 6:827-37
Pfirschke, Christina; Engblom, Camilla; Rickelt, Steffen et al. (2016) Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy. Immunity 44:343-54

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