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Ilan Tsarfaty, PhD
Associate Professor, Department of Human Microbiology
Sackler School of Medicine
Tel Aviv University
Tel Aviv, Israel
Impact: Drs. Tsarfaty, Vande Woude, and Graveel 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. Tsarfaty, Vande Woude, and Graveel 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. 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 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. Ilan Tsarfaty received his BSc. (1983), MSc. (1986) and PhD (1990) from Tel Aviv University. From 1991-1994, he served as a postdoctoral research associate at the National Cancer Institute's Frederick Cancer Research and Development Center. He was a visiting scientist at the Van Andel Research Institute Grand Rapids MI as a part of the Molecular Imaging Center University of Michigan (2001 - 2003). Dr. Tsarfaty has been a member of the Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University since 1994. He is the author of over 50 scientific research articles and over 10 books chapters. Dr. Tsarfaty cloned the gene of the breast cancer antigen Muc1 and showed its potential use as a marker for breast cancer. He was the first to show that the Met tyrosine kinase growth factor receptor is involved in tubule formation in mammary tubule and in mesenchymal epithelial cell conversion.
Dr. Tsarfaty was the first to show that Met is a prognostic factor for breast cancer patients. He also showed that HGF/SF alters metabolic activity by induction of Mimp a novel gene that is involved in metastasis that was cloned and characterize in Dr. Tsarfaty's lab. Dr. Tsarfaty has been leading an effort to develop noninvasive breast tumor molecular imaging modalities as a powerful tool in understanding the metabolic activity induced by Met signal transduction. This technology enhances definition of tumor margins and may allow earlier detection of smaller tumor and small metastatic lesions. Currently, Dr. Tsarfaty's lab is in the process of understanding the physical, cellular and molecular mechanism of Met induced motility leading to embryo development and metastasis.