The Brekken laboratory is located in the Hamon Center for Therapeutic Oncology Research and studies tumor - host interactions with a particular emphasis on extracellular matrix (ECM) and angiogenesis. The biology of metastasis is the central focus for the lab. The lab studies how angiogenesis and ECM remodeling are key components of the metastatic cascade. Current projects are focused on the function of matricellular proteins (e.g., SPARC and fibulin-5) as regulators of ECM remodeling and angiogenesis.
Another major area of study in the lab is the development and evaluation of novel therapy for cancer with a particular focus on anti-angiogenic strategies. Vascular endothelial growth factor (VEGF) is a primary stimulant of blood vessel growth in tumors and as such is a relevant target for anti-angiogenic intervention. Currently we are studying the mechanism of anti-VEGF therapy and how inhibition of VEGF activity affects the tumor microenvironment.
RESEARCH INTERESTS
Tumor - Host Interaction
Angiogenesis
Extracellular Matrix
Metastasis
Monoclonal Antibody Development
RECENT PUBLICATIONS
Brekken, R.A., Poulakkainen, P., Workman, G., Graves, D.C., Lubkin, S.R. and Sage, E.H., "Enhanced growth of tumors in SPARC - null mice is associated with changes in the extracellular matrix." Journal of Clinical Investigation, 111:487-495, 2003
27. Fleming JB, Shen G, Holloway SE, Davis M, and Brekken RA., "Molecular consequences of silencing mutant K-ras in pancreatic cancer cells: justification for K-ras directed therapy." Molecular Cancer Research, 3:413-423, July 2005
30. Beck, AW., Luster, T., Miller, AF., Holloway, SE., Conner, CR., Thorpe, PE., Fleming, JB., and Brekken, RA., "A monoclonal anti-phosphatidylserine antibody in combination with gemcitabine strongly inhibits the growth and metastasis of orthotopic pancreatic tumors in mice." The International Journal of Cancer, 118:2639-2643, May 2006
6. Holloway, SE., Beck, AW., Shivakumar, L., Shih, J., Fleming, JB., and Brekken, RA, "Selective blockade of VEGF Receptor 2 with an antibody against tumor-derived VEGF controls the growth of human pancreatic adenocarcinoma xenografts" Ann Surg Onc, 13:1145, 2006
7. Korpanty, G., Carbon, JG., Grayburn, PA., Fleming, JB., and Brekken, RA, "Monitoring response to anti-cancer therapy by targeting microbubbles to tumor vasculature" Clin Can Res, 13:323, January 2007
SIGNIFICANT PUBLICATIONS
Brekken, R.A., Huang, X., King, S.K., and Thorpe, P.E., "Vascular endothelial growth factor as a marker of tumor endothelium." Cancer Research, 58:1952 - 1959, 1998
Bergers, G., Brekken, R., Vu, T.H., Itoh, T., Tamaki, K., Tanazawa, K., Thorpe, P., Itohara, S., Werb, Z., and Hanahan, D., "Gelatinase B triggers the angiogenic switch during carcinogenesis." Nature Cell Biology, 2:737 - 744, 2000
Brekken, R.A., Overholser, J.P., Stastny, V.A., Waltenberger, J., Minna, J.D., and Thorpe, P.E., "Selective inhibition of VEGFR2 activity by a monoclonal anti - VEGF antibody blocks tumor growth in mice." Cancer Research, 60:5117 - 5124, 2000
Puolakkainen*, P., Brekken*, R. A., Muneer, S., and Sage, E. H., "Enhanced growth of pancreatic tumors in SPARC-null mice is associated with decreased deposition of extracellular matrix and reduced tumor cell apoptosis" Molecular Cancer Research, 2:215-224, May 2004
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