Scientist, Department of Integrative Oncology, Radiation Biology Unit, BC Cancer Agency (2011)
Assistant Professor, Department of Pathology and Laboratory Medicine, University of British Columbia (2011)
Faculty Associate Member, Interdisciplinary Oncology Program, Faculty of Graduate and Postdoctoral Studies, UBC
Dr. Kevin Bennewith obtained his PhD in Pathology and Laboratory Medicine at UBC in 2004 under the supervision of Dr. Ralph Durand at the BC Cancer Agency. During his PhD training, he studied solid tumour physiology with particular emphasis on quantifying poorly oxygenated (hypoxic) tumour cells. He then joined the laboratory of Dr. Amato Giaccia at Stanford University as a post-doctoral scholar, where he was involved in several projects investigating the role of hypoxia-induced secreted proteins in the growth and metastasis of solid tumours. His post-doctoral work included studying the role of connective tissue growth factor in pancreatic tumour growth and using an orthotopic pancreatic tumour model to study the efficacy of chemotherapeutics designed to target hypoxic tumour cells. He also helped to discover a central role for lysyl oxidase in breast cancer metastasis through promoting the recruitment of bone marrow-derived cells to metastatic target organs. Dr. Bennewith was recruited to the BC Cancer Agency in 2008, and since that time his work has been funded by a Terry Fox Foundation New Investigator Operating Grant, the Canadian Institutes of Health Research Institute of Cancer Research, the BC Cancer Foundation, and a Michael Smith Foundation for Health Research Career Investigator Award. Dr. Bennewith is currently a Scientist at the BC Cancer Agency and an Assistant Professor in Pathology and Laboratory Medicine at UBC.
- PhD, The University of British Columbia,Pathology and Laboratory Medicine. 2004
- BSc, The University of British Columbia, Chemistry. 1997
- Cancer research
- Solid tumour microenvironment
- Metastasis research
- Pre-metastatic niche
- Targeting hypoxic tumour cells in therapy
- Radiation biology
- 2013-present, National Mentor, The Terry Fox Foundation Strategic Initiative for Excellence in Radiation Research for the 21st Century (EIRR21) at CIHR
- This integrated Radiation Medicine training program for graduate students and post-doctoral fellows is based out of the University of Toronto, with 32 “local” mentors from Toronto, 3 national mentors from across Canada, and 3 international mentors. I am the national mentor representing the province of British Columbia
Most solid tumours contain cells that are poorly oxygenated, and these hypoxic tumour cells are refractory to a variety of cancer treatments including radiation therapy and chemotherapy. Not only are hypoxic cells the most difficult tumour cells to kill with conventional therapies, but hypoxia also promotes a more aggressive tumour phenotype. In the clinic, patients with primary tumours that contain large fractions of hypoxic cells have poor outcome, due in large part to limited treatment response and the presence of distant metastatic disease. My lab is interested in the role of tumour hypoxia (and the tumour microenvironment) in cancer therapy and in the development of tumour metastases.
Quantification of Tumour Hypoxia
The extent of hypoxia in solid tumours can be measured by exogenous hypoxia markers (drugs that are bound and retained in hypoxic cells) and/or endogenous hypoxia markers (proteins that are increased in hypoxic cells). The oxygenation level of tumour cells can change as a function of time, and this transient (or cyclic) hypoxia is poorly understood. We use immunohistochemistry and flow cytometry to identify and quantify transiently hypoxic tumour cells with the goal of designing more effective therapeutic strategies to target (or exploit) tumour hypoxia.
Bone marrow-derived cells in solid tumour metastasis
The metastatic spread of cancer is associated with over 90% of cancer-related deaths. We have found that selected proteins secreted by tumours can stimulate the accumulation of bone marrow-derived cells (BMDCs) in tissues prior to the arrival of metastatic tumour cells. BMDC accumulation may enhance the survival and growth of metastatic tumour cells, and predict future sites of metastatic tumour growth. We are particularly interested in the accumulation and function of immune suppressive myeloid cells (myeloid-derived suppressor cells, macrophages) in metastatic target organs, and in therapeutic modification of tumour-secreted proteins and immune suppressive cells in metastatic-target organs to decrease metastatic tumour growth.
We gratefully acknowledge operating grant funding and stipend support from the following organizations:
The Canadian Institutes of Health Research (http://www.cihr.gc.ca/e/193.html)
The BC Cancer Foundation (http://www.bccancerfoundation.com/)
The Canadian Institutes of Health Research: Institute of Cancer Research (http://www.cihr-irsc.gc.ca/e/12506.html)
Stipend and salary support:
Kevin Bennewith is a Michael Smith Foundation for Health Research Biomedical Research Scholar (http://www.msfhr.org/)
Jenna Collier is currently funded by a Walter C. Koerner Fellowship from the UBC Affiliated Fellowships Program (https://www.grad.ubc.ca/awards/affiliated-fellowships)
Jenna Collier and Liz Halvorsen were funded by Frederick Banting and Charles Best Canada Graduate Scholarships Master’s Awards from the Canadian Institutes of Health Research (http://www.cihr-irsc.gc.ca)
Natalie Firmino is currently funded by a Cordula and Gunter Paetzold PhD Fellowship from the UBC Affiliated Fellowships Program (https://www.grad.ubc.ca/awards/affiliated-fellowships)
Natalie Firmino and Brennan Wadsworth are Scholars in The Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) Program (http://www.radonc.utoronto.ca/stars21)
Liz Halvorsen is currently funded by a Li Tze Fong Memorial Fellowship from the UBC Affiliated Fellowships Program (https://www.grad.ubc.ca/awards/affiliated-fellowships)
Liz Halvorsen and Brennan Wadsworth are currently funded by Four Year Doctoral Fellowships from the University of British Columbia (https://www.grad.ubc.ca/awards/four-year-doctoral-fellowship-4yf)
Brennan Wadsworth was funded by an Alexander Graham Bell Canada Graduate Scholarship Master’s Award from the National Sciences and Engineering Research Council of Canada (http://www.nserc-crsng.gc.ca/index_eng.asp)
Brennan Wadsworth was funded by a Northern Telecom Graduate Fellowship and a Jean MacDonald Graduate Fellowship from the University of British Columbia Affiliated Fellowship Program (https://www.grad.ubc.ca/awards/affiliated-fellowships)