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George F. Vande Woude, PhD
Distinguished Scientific Fellow
Van Andel Research Institute
Grand Rapids, Michigan
Goal: To identify novel targets for the treatment of metastatic breast cancer.
Impact: Drs. Vande Woude, Tsarfaty, and Graveel are investigating how a gene called MET promotes the spread of breast cancer (metastasis) and resistance to therapy in patients with aggressive breast cancers. They hope to identify biomarkers of response to therapy and identify new approaches for preventing metastasis.
What’s next: The team will continue to pursue genes that play a role in breast cancer risk and treatment resistance.
In order for breast cancer to spread to other locations in the body, cancer cells must break away from the primary tumor and travel through the blood or lymph system before invading distant tissues. Oncogenes are genes with potent tumor promoting effects. Drs. Vande Woude, Tsarfaty, and Graveel are studying the oncogene MET which promotes metastasis and resistance to treatment. They are using laboratory models to investigate how MET drives these activities in aggressive forms of breast cancer.
Full Research Summary
Research area: To understand how tumors spread to other tissues and identify new targets for therapeutic development.
Impact: Breast cancers that spread to other tissues—a process called metastasis—have evolved to gain a survival advantage that makes them resistant to cancer therapies. There is no cure for metastatic breast cancer and an urgent need to find effective therapies to both prevent breast cancer from spreading and treating it in those diagnosed with metastatic breast cancer. The research team of Drs. Tsarfaty, Vande Woude and Graveel have been studying a potent driver of metastasis called MET. With BCRF support, their work has led to new insights into the activity of MET in promoting the motility and survival of cancer cells and identified other genes that partner with MET in its metastatic program. Collectively, their work is increasing our understanding of how cancer cells gain the ability to spread and form new tumors and will inform new strategies to treat and prevent metastatic breast cancer.
Current research: The research team will continue ongoing studies using specially designed laboratory models to delineate the role of MET in breast cancer metastasis.
What they’ve learned so far: In the last year, the team identified several genes that modify the ability of MET to promote breast cancer initiation and progression; defined several metastasis-promoting programs activated by MET; and discovered that MET expression is found at high levels in some tumors from patients with estrogen receptor-positive and triple-negative breast cancers.
What’s next: Using their unique laboratory models and expertise they will identify and characterize the modifier genes that promote MET-mediated tumorigenicity. The relevance of these modifier genes will be examined in human breast cancers. They will further interrogate the role of MET inhibitors in aggressive breast cancer. Overall, these studies will provide an unprecedented view of the genes that influence breast cancer tumor initiation and progression and identify potential prognostic signatures and therapeutic targets.
Dr. George F. Vande Woude received his M.S. (1962) and PhD (1964) from Rutgers University. From 1964-1972, he served first as a postdoctoral research associate, then as a research virologist for the US Department of Agriculture at Plum Island Animal Disease Center. In 1972, he joined the National Cancer Institute and from 1983-1998 was the Director of the Advanced Bioscience Laboratories-Basic Research Program. In 1993, he was elected to the National Academy of Sciences and served as Chair of the Section for Medical Genetics, Hematology & Oncology (2004-2007). In 1999, he became the first Director of Van Andel Research Institute (VARI), a position he held until February 2009. He is currently a Distinguished Scientific Fellow at VARI.
Since the 1970s Dr. Vande Woude’s laboratory research has focused on understanding the molecular basis of cancer. Dr. Vande Woude’s laboratory was first to determine the structure and enhancer function of proviral long terminal repeats (LTR) and the first to demonstrate that a normal cellular protooncogene could be activated as an oncogene. These findings provided a foundation for the search for active oncogenes in tumors. In 1984, Dr. Vande Woude discovered human Met oncogene, a member of the tyrosine kinase growth factor receptor family that is altered in the majority of cancers. In addition to many basic scientific discoveries, his laboratory has also generated novel tools to help with drug development. Currently, his lab is developing novel preclinical models for evaluating the efficacy of tyrosine kinase inhibition in cancer patients.