Funded Research Points to New Breast Cancer Detection and Therapy Stratagies
October 21, 2004—Oakland, CA—Jan Schnitzer, M.D., and his team at the Sidney Kimmel Cancer Center in San Diego recently developed and tested a new way to find and treat breast cancer. His group is using a targeted method that looks at the surface proteins of tumor blood vessels instead of targeting the tumor cells, which are often inaccessible to imaging agents and drug therapies.
Results of the study were published in Nature 429:629-635 (2004) and became the #1 most-downloaded article in June. Dr. Schnitzer’s article was also favorably featured in a “News and Views” review in Nature 429:618-619 (2004), which said, “...we might be able to use the writing on the vessel wall both to design unique molecular tools by which to recognize specific diseases, and to direct therapies to specific organs thereby avoiding sending drugs as unwanted ‘spam’ to all other organs in the body. For instance, proteins in the vasculature of tumors could enable imaging agents to locate growing malignancies, and drugs to specifically inhibit the tumor's endothelial cells and so prevent further tumor growth.”
The aim of Dr. Schnitzer’s study is to identify protein components that distinguish tumor-associated endothelial cells from other, healthy endothelial cells in the body. The team’s strategy focused on a specific portion of the endothelial cell, called caveolae, which are small invaginations of the cell surface that carry out transport and signaling functions in cells. Using protein purification, proteomic, and advanced informatics methods, they ultimately found a group of 12 proteins that served as selective markers of the tumor-associated vasculature. For one of these proteins, called Annexin A1, Dr. Schnitzer's group was able to generate monoclonal antibodies. When appropriately labeled with radioactive iodine, anti-annexin A1 injected into the bloodstream was able to visualize tumors by whole-body planar γ-scintigraphic imaging. In addition, they were able to shrink tumors, showing the potential of their strategy for radio-immunotherapy. It is likely that successfully targeting the normal endothelial cells of the tumor vasculature will avoid the genetic heterogeneity and drug resistance problems seen when therapies are directed at tumor cells themselves. This approach seems ideal for detecting and treating metastatic disease where tumors are not often amenable to surgery.
The California Breast Cancer Research Program funded Dr. Schnitzer through two separate grants in 1999 and 2002, which allowed him to develop the concept and methodology, then validate it in tumors grown in animal models. Dr. Schnitzer's research was also funded by the National Institutes of Health (Heart, Lung and Blood), National Cancer Institute, and the California Tobacco-related Disease Research Program.
You can read more details of this research on the CBCRP Web site (http://www.cbcrp.org/research/PageInvestigator.asp?person_id=551) and Dr. Schnitzer's Web site (http://www.skcc.org/schnitzer.html).
About the CBCRP
The mission of the California Breast Cancer Research Program is to eliminate
breast cancer by leading innovation in research, communication, and collaboration
in the California scientific and lay communities.
Created by the State Legislature in 1993, the California Breast Cancer Research Program (CBCRP) is the largest state-funded breast cancer research program in the nation and is administered by the University of California, Office of the President. To date, the CBCRP has awarded 617 grants to 70 scientific institutions and community entities, totaling more than $150 million for research in California to prevent, treat, and cure breast cancer. Grants from the CBCRP fill gaps not traditionally funded by other research programs to jump-start new areas of investigation that push the boundaries of research and foster new collaborations. The CBCRP is funded through the voluntary tax check-off program on personal income tax form 540, a portion of the state tobacco tax, and individual contributions. For more information call 888 313-2277, or visit www.cbcrp.org.
