Robert A. Weinberg, PhD

2009-2010 BCRF Project:
Dr. Weinberg's research has demonstrated that breast cancer is a systemic disease long before primary tumors spread by metastasis to distant sites in the body. In particular, his group finds that primary tumors stimulate the bone marrow to produce and release into the circulation certain cells that can then be recruited by cancer cells throughout the body. Once recruited, these cells then empower the growth of the cancer cells.

This discovery has multiple possible implications. It suggests that primary tumor actively promote the growth of distantly located nests of metastatic cells and that this stimulation might be blocked through the use of a monoclonal antibody that binds and neutralizes a signaling molecule in the circulation that is required for this stimulation. Second, it may enable researchers to construct models that allow the growth of many types of human breast cancer cells that otherwise have been very difficult to propagate in models, depriving investigators of good ways of predicting the behavior of these tumor types when they are growing in patients. Third, they are investigating the possibility that the creation of major wounds in a host may stimulate the growth of otherwise-slowly growing breast cancer nests, in parallel with the work described above. If effects are observed, this holds implications for the influence of surgery on the outgrowth of residual tumor cells that have not been removed by such surgery.

Mid-Year Progress Report:
Most studies of the biology of breast cancer have focused on the interactions between nearby cells that are located within primary tumors. However, Dr. Weinberg's evidence indicates that primary tumors also change the entire biology of the tumor-bearing host, doing so in order to facilitate their own growth. Thus, breast cancer cells are able to change the make-up of cells in the bone marrow, causing the marrow to produce and release cells into the circulation that then stimulate the growth of the primary tumor or its distantly located metastatic derivatives. The Weinberg lab has found at least two mechanisms by which the primary tumor does so. Each of these signaling mechanisms, which operate by releasing signaling factors into the circulation, represents an area of possible therapeutic intervention, since such factors can be neutralized by appropriate monoclonal antibodies, thereby cutting off vital supply lines on which the primary tumor and its metastases depend.

Bio:
Dr. Weinberg is a founding member of the Whitehead Institute for Biomedical Research and the Daniel K. Ludwig Professor for Cancer Research at the Massachusetts Institute of Technology (MIT). He is also the first Director of the Ludwig Cancer Center at MIT. He is an internationally recognized authority on the genetic basis of human cancer.

Dr. Weinberg and his colleagues isolated the first human cancer-causing gene, the ras oncogene, and the first known tumor suppressor gene, Rb, the retinoblastoma gene. The principal goal of his research program is to determine how oncogenes, their normal counterparts (proto-oncogenes), and tumor suppressor genes fit together in the complex circuitry that controls cell growth. More recently, his group has succeeded in creating the first genetically defined human cancer cells. He is particularly interested in applying this knowledge to improve the diagnosis and treatment of breast cancer.

Dr. Weinberg is the author or editor of six books and more than 350 articles. He has written a comprehensive cancer textbook entitled "The Biology of Cancer". His other books, intended for a lay audience, are "One Renegade Cell," "Racing to the Beginning of the Road: The Search for the Origin of Cancer" and "Genes and the Biology of Cancer," co-authored with Dr. Harold E. Varmus, former Director of the National Institutes of Health. He is an elected Member of the U.S. National Academy of Sciences and Fellow of the American Academy of Arts and Sciences. He is a Member of the American Philosophical Society and the Institute of Medicine.

Among Dr. Weinberg's many honors and awards are the Discover Magazine 1982 Scientist of the Year, the National Academy of Sciences/U.S. Steel Foundation Award in Molecular Biology, the Sloan Prize of the General Motors Cancer Research Foundation, the Bristol-Myers Award for Distinguished Achievement in Cancer Research, the Harvey Prize from the American Society for Technion Israel Institute of Technology, the Gairdner Foundation International Award, the Keio Medical Foundation Prize, the 1997 National Medal of Science, the City of Medicine Award and the 2004 Wolf Foundation Prize and the Prince of Asturias Science Prize. He has served on scientific advisory boards for the Institute of Molecular Pathology in Vienna, Austria, the Weizmann Institute in Rehovot, Israel, and the Massachusetts General Hospital in Boston.

Born in Pittsburgh in 1942, Dr. Weinberg received his B.S. (1964) and Ph.D. (1969) degrees in Biology from MIT. He did postdoctoral research at the Weizmann Institute and the Salk Institute in La Jolla, California, and then returned to MIT in 1972. In 1982, he was appointed Professor of Biology at MIT.