Robert A. Weinberg, PhD

2012-2013 BCRF Project:
The origin of aggressive breast cancers can be traced to a change that breast cancer cells undergo as they evolve from a more benign to a more malignant, aggressive state. This change, termed the epithelial-mesenchymal transition (EMT), confers on them traits such as movement, invasiveness, a resistance to therapy, and an ability to renew themselves - the last trait associated with the behavior of cancer stem cells. The latter, which serve as the pioneers of new metastases, are more resistant to therapy and must be eradicated in order to prevent the delayed relapses that threaten many women who are initially treated and ostensibly cured of breast cancer. Dr. Weinberg's BCRF-funded study addresses the origins of these cancer stem cells and how their development may be prevented within tumors. Dr. Weinberg's team intends to map out in greater detail the interactions between the epithelial vs. the mesenchymal cell phenotype and the stem-cell state. Their recent research findings indicate that cells that have proceeded too far into the mesenchymal state become "trapped." The outcomes of this work hold critical implications for the molecular mechanisms that generate breast cancer stem cells and for the organization of the stem cells in the normal mammary gland.

Independent of this, Dr. Weinberg's team is interested in utilizing the recently gleaned research findings about the contextual signals that generate an EMT and the signaling pathways that operate within breast cancer stem cells in order to develop therapeutic strategies that may one day prove clinically useful in treating aggressive breast cancers.

Mid-year Progress: The acquisition by breast cancer cells of aggressive properties allows them to become invasive and to metastasize to distant tissues, yielding the metastases that are responsible for essentially all of breast cancer-associated deaths. However, the precise mechanisms by which these cells acquire aggressive traits have been elusive until recently. It is clear that these cancer cells do not do so on their own. Instead, they respond to signals released by non-cancer cells found nearby within breast tumors, the latter cells forming the "stroma" of breast cancers. These stromal cells are recruited into tumors and, once present, proceed to release signals that persuade the breast cancer cells to develop aggressive traits. Dr. Weinberg's laboratory continues to identify some of the responsible stromal cells for this development and examine their precise contributions to this malignant progression. Knowledge of these interactions should, in the future, enable new types of therapy to be developed that block these interactions and thereby prevent the acquisition of invasive and metastatic traits by breast cancer cells.

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 BS (1964) and PhD (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.

Read more about Dr. Weinberg's work in the August 16, 2011 issue of The New York Times.
Additional article in The Wall Street Journal.