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analysis: exClUSIve
World
leaders
in the
fight
against
cancer
Could you begin with a broad overview of the Princess Margaret
Cancer Centre? What role does it play within the University
Health Network (UHN)?
The Centre is the largest cancer research centre in Canada, and one
of the largest in North America. We see 19,000 patients a year;
13,000 of them with new cancers. We also have one of the largest
radiotherapy centres in the world. We have a research institute, the
Ontario Cancer Institute, with 65 independent laboratories and
several cores. We also have an extremely active clinical research
programme, with 165 clinician-investigators. On a yearly basis,
about 25-30 per cent of our patients are on some form of clinical
trial. We are the host institution for US National Cancer Institute
(NCI)-funded Phase I and Phase II consortia – the only such sites
located outside of the US. We also are the only member of the
newly formed NCI Immune Therapy Network outside of the US. The
History
of Princess Margaret Hospital
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Founded as the Ontario Cancer
Institute by the Ontario government
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14 international INNOvATION
Officially opened by HRH
Princess Margaret. Renamed
Princess Margaret Hospital
Breakthroughs
Wide use of cobalt radiotherapy for cancer
Evidence that radiation can cure Hodgkin’s disease
D r
Benjamin
Neel
Director, Ontario Cancer Institute,
Princess Margaret Cancer Centre
Established more than 50 years ago,
the Princess Margaret Cancer Centre
now stands as the largest cancer
research centre in Canada and one
of the world’s top five. Dr Benjamin
Neel highlights some of the Centre’s
key accomplishments over the past
decade, its ongoing programmes and
ambitious plans for the future
Princess Margaret Cancer Centre is part of UHN – which also includes
Toronto General Hospital, Toronto Western Hospital and Toronto
Rehabilitation Institute. The Centre is the only one to specialise in
cancer medicine and research. All four hospitals are affiliated with
the University of Toronto.
The Centre is ranked as one of the world’s top five research
centres. How has it gained such a strong reputation?
This rating is based on a number of metrics, which include the
percentage of high-impact papers and highly-cited papers, research
funding, and clinical trials that lead to changes in clinical practice.
Historically, major discoveries in basic cancer research (eg. the T
cell receptor, the stem cell and the cancer stem cell), as well as
translational/clinical research (eg. localised radiotherapy for breast
cancer, practice standards for lung, pancreas and other cancers,
Pioneered use of conservative surgery (lumpectomy)
to treat breast cancer
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Discovery of blood-forming stem
cells enabling bone marrow
transplants
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Identified P-glycoprotein as
a major cause of cancer drug
resistance

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20 November, 2006
Rare stem cells
found to cause colon cancer
A groundbreaking study from UHN revealed that stem cells
could be driving colon cancer.
Scientists analysed tumour samples taken from patients with colon
cancer and implanted them into mice with immune deficiency to see
how different cancer cells behaved, and if some were more likely than
others to produce tumours.
The results revealed that not all cancer cells behaved the same and that
stem cells were, in fact, responsible for generating the tumours in
mice. They also discovered that cancer-promoting stem cells were
rare – one in every 57,000 cancer cells. “We found that not every
tumour cell is equally capable of sustaining tumours in the
colon,” explains Principal Investigator of the research
and Senior Scientist at Ontario Cancer Institute, Dr
John Dick. This finding could point the way to
new treatments in the fight against
cancer.
18 January, 2007
Breast density the #1
risk factor for breast cancer
The Campbell Family Institute for Breast Cancer Research
at Prince Margaret discovered that breast cancer risk was
almost five times greater in women with extensive dense tissue
in the breast compared to those with little or no dense tissue. As
risk remained high over a period of eight years, both at screening
and between screens, the results show that in addition to increasing
risk of breast cancer, dense breast tissue also makes cancers more
difficult to see in a mammogram.
“This study establishes that breast density is an extremely
important risk factor for developing breast cancer,” says principal
investigator Dr Norman Boyd. “Depending on a woman’s
age, between 16-30 per cent of breast cancers can be
attributed to extensive density. Other risk factors,
including family history and the known
genes, account for a much smaller
proportion of the disease.”
Discovery of the T-cell receptor,
significant in the field of immunology
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Reopened by HRH Princess Margaret
at its current location on University
Avenue, College Street, Toronto
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Developed a chemotherapy treatment
for hormone-resistant prostate cancer
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Recent milestones
mammographic density as a major cancer risk factor), were made at the
Princess Margaret and its research arm, the Ontario Cancer Institute.
What would you cite as your greatest achievements over the
past 10 years?
There are several, but five that spring to mind are:
• Gene signatures for lung cancer and leukaemia that predict outcome
• Purification of the human and mouse hematopoietic stem cells to
homogeneity
• Identification of colon cancer stem cells
• Credentialing of Avastin as the first new therapy for ovarian cancer in
last 20 years
• establishing mammographic density as the most important risk factor
for breast cancer aside from BRCA1/2
What kinds of research programmes are currently being
undertaken at the Centre?
We have major programmes in: normal and cancer stem cells (the
latter focused on leukaemia, colon, head and neck, kidney, and ovarian);
hypoxia, with a particular focus on its role in radiation response;
epigenetics and epigenomics; precision genomic medicine with nextgeneration
sequencing (NGS) partnered to clinical trials and targeted
therapy; cancer immunology/immune therapy; molecular imaging;
image-guided radiotherapy and surgery; and regenerative medicine.
Could you outline the research facilities at the Centre? Do you
have plans to enhance them further in the future?
We are situated in three locations around Toronto’s ‘Discovery District’
– so named because of its high concentration of hospitals and research
institutions (particularly those related to biotechnology) and proximity
to the University of Toronto. This is the district where Drs Banting and
Best discovered insulin in 1922, and Drs Till and McCulloch discovered
stem cells in 1961.
Our research facilities occupy six floors in the main Princess Margaret
buildings at 610/620 University Ave., and five floors in the Toronto
Medical Discoveries Tower (TMDT) building across the street. We plan to
expand TMDT to three additional floors in the summer of 2013. We have
two fully equipped barrier vivaria and flow cytometry facilities at both
locations, as well as a genomics centre, multi-modal animal imaging
Became part of the University Health
Network (UHN) – with Toronto General
Identified gene clusters in lung cancer
using microarray technology
and Toronto Western hospitals – this is the
largest cancer programme in the country
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analysis: exClUSIve
Developed a method for detecting gene
mutations to enhance care for
families with retinoblastoma
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analysis: exClUSIve
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7 September 2010
Gene sequence discovery
to provide roadmap for lung
cancer treatment
UHN scientists pinpointed a gene sequence that
could guide the treatment of patients with a particular
type of lung cancer, finding that the 15-gene signature
could potentially identify patients with early stage nonsmall
cell lung cancer.
This is a major breakthrough in patient care
because up until now doctors have been unable
to predict which patients with early-stage nonsmall
cell lung cancer will benefit from
chemotherapy post surgery.
core, a mass spectrometry facility, NMR spectrometers and x-ray
crystallography and a histology core at TMDT.
We plan to add a mass cytometer to our flow facility and several new
NGS instruments with associated high performance computing to our
genomics capabilities.
Our clinical research space uses over 350 individual outpatient clinics,
imaging, laboratory medicine and pathology facilities.
How does the atmosphere at the Centre foster and enhance the
development of trainee researchers?
The co-localisation of clinician scientists, basic scientists and clinicians
facilitates interactions. We also have a weekly faculty lunch at which an
investigator presents ongoing unpublished research and a yearly retreat
focused on promoting interactions. We also have specific large ($0.5-1
million) translational research grants that must involve at last one basic
scientist and one clinician or clinician-scientist.
What are your goals for future research at the Centre?
• Provide a detailed molecular diagnosis of every patient’s tumour in
real time within five years
• Develop serum/blood-based molecular monitoring
• Increase clinical trials of targeted therapies and targeted
therapeutic combination
Discovery of breast tissue
density as major breast cancer risk
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16 international INNOvATION
Discovery of colon-cancer
causing stem cells
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08
• Increase our presence in immune therapy, including cell-based (TIl)
therapies and immunomodulators
• Increase our expertise in epigenetics and help bring epigenetic therapy
to the clinic
• Increase our molecular imaging expertise and use of molecular
imaging in clinical trials
• Develop improved cancer models, including xenografts and human eS
cell-based models
• Improve therapeutic ratio of clinical interventions with image-guided
therapies
• Bring normal tissue protection and
regeneration into cancer therapeutics
Celebrated its 50 th anniversary. City
of Toronto presented a congratulatory
scroll to mark the occasion
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29 December 2011
New drug gives hope to
ovarian cancer sufferers
An international clinical trial revealed that a new drug,
known as ‘Avastin’, not only halts the progression of
ovarian cancer but may even increase survival rates. The
seven-year study co-led by Drs Amit Oza, Princess Margaret
Cancer Program, UHN and Timothy Perren, St James’s
Institute of Oncology, Leeds, UK found that on average the
cancer was delayed from returning for up to two months.
“This is the first new drug in ovarian cancer in 15 years to
improve outcome and I believe it should be considered
as a potential new standard of care,” Oza enthused.
The results also suggest that the drug could
prolong patients’ lives and the extent of
this possibility is currently under
investigation.
www.theprincessmargaret.ca
Treated more than 350,000 new
cancer patients since it first opened
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Renamed the Princess Margaret Cancer
Centre, one of the Top 5 comprehensive
cancer centres in the world