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George F. Vande Woude, PhD
Distinguished Scientific Fellow
Van Andel Research Institute
Grand Rapids, Michigan
Impact: Drs. Vande Woude, Graveel, and Tsarfaty are investigating how a gene called MET and partner oncogenes promote 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 a detailed understanding of 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, Graveel, and Tsarfaty are studying the oncogene MET which promotes metastasis and resistance to treatment. They are using laboratory models to investigate how MET and other oncogenes drive 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 and treating it. The research team of Drs. Vande Woude, Graveel, and Tsarfaty 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 to promote metastasis. 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 Investigation: The research team will continue ongoing studies using specially designed laboratory models to delineate the role of the oncogenes MET, p53, mutant BRCA1, and NF1 in breast cancer therapy resistance and metastasis.
What they’ve learned so far: In the last year, the team characterized a novel, MET-induced aggressive subgroup of triple-negative breast cancer cells; defined several mechanisms of MET-induced metabolic reprogramming; and identified several genes that modify the ability of MET to promote breast cancer initiation and progression.
What’s next: Using their unique laboratory models and expertise they will identify and characterize the molecular mechanisms of MET-induced plasticity of breast cancer cells, which enables metastasis. Additionally, they will interrogate the role of MET, p53, mutant BRCA1, and NF1 genes that drive breast cancer resistance and metastasis. 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.