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Sunnybrook Research Institute
Robert Kerbel PhD
Senior Scientist
Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room S2 17
Toronto, ON
M4N 3M5 Phone: 416-480-5711
Fax: 416-480-5884
Administrative Assistant: Cassandra Cheng
Phone: 416-480-6100, ext. 3537
Email: cassandra.cheng@sunnybrook.ca
Education:
- BA, 1968, Life Sciences, University of Toronto, Canada
- PhD, 1972, Microbiology and Immunology, Queen's University, Canada
Appointments and Affiliations:
- Senior scientist, molecular and cellular biology - Odette cancer research program, Sunnybrook Research Institute
- Professor, lab medicine and pathobiology, medicine, University of Toronto
- Professor (adjunct), cancer biology, medicine, MD Anderson Cancer Center, University of Texas
- Professor, medical biophysics, University of Toronto
- Co-director, Toronto Angiogenesis Research Centre
- Canada Research Chair in Tumour Biology, Angiogenesis and Antiangiogenic Therapy, Tier 1
Research Focus:
- Translational research studies of antiangiogenic therapy for the treatment of metastatic disease
Research Summary:
The Kerbel laboratory is at the forefront of a promising new paradigm for the treatment of cancer: antiangiogenic therapy. Following decades of research by many groups, the first antiangiogenic drug (Avastin) for the treatment of (colorectal) cancer was recently approved by the United States Food and Drug Administration. This sets the stage for a new era of a fundamentally different approach for the treatment of cancer.
As such, it highlights the need to study a number of questions including the following:
- What factors regulate tumor angiogenesis?
- What are the best targets for antiangiogenic drugs?
- What is the best way to combine these drugs with chemotherapy or other therapeutic modalities?
- How can we determine, using cellular, molecular or imaging 'surrogate' markers, the optimum doses for such drugs and monitor antiangiogenic activity?
- What are the mechanisms of response and resistance to antiangiogenic drugs?
- What are the best preclinical models to test antiangiogenic drugs, especially from the viewpoint of metastatic disease?
The Kerbel laboratory is studying all of these questions, with the greatest emphasis on metronomic low-dose or antiangiogenic chemotherapy. This refers to the use of relatively non-toxic low doses of conventional, chemotherapeutic drugs, given frequently, with no prolonged interruptions. It is thought that chemotherapy administered in this way targets the growing neovasculature of tumors, and is ideal to use in combination with new, targeted antiangiogenic drugs such as the humanized anti-VEGF antibody, Avastin.
The metronomic therapy concept, co-pioneered in the Kerbel laboratory, has sped into clinical trial testing in centres throughout Canada, the United States and Europe. The lab is involved in some of these, mostly those to do with the development and use of new surrogate biomarkers. The approach is an excellent example of translational research; that is, discoveries made in the laboratory that can be moved rapidly into the clinic.
Selected Publications:
See current publications list at PubMed.
- Man, S., Bocci, G., Francia, G., Green, S., Jothy, S., Bergers, G., Hanahan, D., Bohlen, P., Hicklin, D., and Kerbel, R. (2002) Anti-tumor and anti-angiogenic effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. Cancer Res., 62: 2731-2735.
- Bocci, G., Nicolaou, K.C., and Kerbel, R. (2002) Protracted low-dose effects on human endothelial cell proliferation, adhesion and migration in vitro reveals a potential "antiangiogenic window" for chemotherapeutic drugs. Cancer Res., 62: 6938-6943.
- Kerbel, R.S. and Folkman, J. (2002) Clinical translation of angiogenesis inhibitors. Nature Reviews Cancer, 2: 727-739.
- Bocci, G., Francia, G., Man, S., Lawler, J., and Kerbel, R.S. (2003) Thrombospondin-1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc. Nat'l Acad. Sci. (USA), 100: 12917-12922.
- Viloria-Petit, A., Miguerol, L., Yu, J.L., Gertenstein, M., Sheehan, C., May, L., Henkin, J., Lobe. C., Nagy, A., Kerbel, R.S., and Rak, J. (2003) Contrasting effects of VEGF gene disruption in embryonic stem cell-derived versus oncogene-induced tumors. EMBO J., 22: 4091-4102.
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