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Innovative new investigators to study cancer growth and response to treatment

March 06, 2014

Three promising Canadian cancer researchers, two in Ontario and one in Quebec, have been awarded a total of $1.35 million under the Terry Fox Research Institute’s 2013 New Investigator Awards.

 Dr. Paul Boutros    Dr. Catherine O'Brien    Dr. Franics Rodier
(From left) Dr. Paul Boutros, Dr. Catherine O'Brien and Dr. Franics Rodier are TFRI's New Investigator Awardees for 2013

University Health Network researchers Drs. Paul Boutros and Catherine O’Brien and Dr. Francis Rodier, Centre de recherche du Centre hospitalier de l’université de Montréal (CRCHUM), were selected by a committee of international scientific experts in a competitive application process. Each will now be mentored within a team of Terry Fox-funded discovery or translational research projects where they will work with leading cancer researchers.

Each investigator will use a different approach and technique to try to uncover more about how cancers grow and respond to treatments. Their goal is to learn why some cancers respond better to therapy than others.

Dr. Victor Ling, TFRI president and scientific director, explains why their work is important. “There can be big differences not only between cancers, but within a cancer tumour and between single cancer cells. I’m very excited to see how these three young investigators progress and what they find out.”

The funding for the three investigators will be provided over the next three years. The New Investigators program is an annual competition and provides research operating grant support to future leaders as they develop their independent careers in cancer research.

 

Dr. Paul Boutros
Ontario Institute for Cancer Research

Project Title: Systems Biology of Tumour Hypoxia
Award: $450,000
Mentoring Program: The Terry Fox New Frontiers Program Project Grant: Hypoxia in Tumours: Clinical and Experimental Studies
Mentors/PIs: Dr. Bradly Wouters and Dr. Robert Bristow

Dr. Paul Boutros is a computational biologist and principal investigator with the Ontario Institute for Cancer Research. Using his mathematical expertise, Dr. Boutros will take a computational approach to modeling the internal structure or “micro-environment” of a tumour, with the goal of predicting how a tumour will respond to therapy.

“Tumours that look superficially very similar can have very different responses to treatment,” he explains. “Some areas within a tumour grow quickly and others grow slowly. In particular, different parts of a tumour show differences in blood circulation and in oxygenation. Tumours with blood vessels that are inefficient at providing oxygen respond very poorly to many therapies. By creating models of the tumour micro-environment and bringing different data sets together, I hope to find a link between genetics and tumour oxygenation.”

As part of the TFRI Hypoxia in Tumours Program Project Grant, Dr. Boutros will have access to 15 years’ worth of unique data collected from several projects. “By combining everything we know about a tumour, in the future we may be able to predict how a patient will respond to treatment, potentially enabling us to modify existing therapies and treat patients more effectively.”

Being part of TFRI is critical to Dr. Boutros’ work. He says “I am able to learn so much from colleagues with more experience and scientific backgrounds that are different from mine. They help me apply clinical meaning to my mathematical work. Being part of the TFRI community not only helps me, but my research team and trainees all benefit greatly as well. ”

Dr. Rob Bristow, Princess Margaret Cancer Centre, says “The merging of our many datasets collected over the years will lead to a better understanding of tumour biology and prognosis. Dr. Boutros is an outstanding addition to our PPG team and he fills an important gap in bioinformatics across all our projects.”

 

Dr. Catherine O’Brien
University Health Network

Project Title: Understanding Cancer Stem Cell Heterogeneity and Dynamics: Implications for Therapy in Human Colorectal Cancer
Award: $450,000
Mentoring Program: The Terry Fox New Frontiers Program Project Grant: Addressing tumour heterogeneity through identification of subgroup-specific "shared maintenance genes" - the right target for each cancer
Mentor/PI: Dr. Sean Egan

Dr. Catherine O’Brien is a scientist with the Ontario Institute for Cancer Research and a general surgeon with the University Health Network. She is studying colorectal cancer at the level of single cells to identify which cells cause metastases and are resistant to chemotherapy.

“We have known for a long time that not all cells in any given cancer are the same – some cancer cells are more aggressive than others. We also know that cancer cells from the same tumour can demonstrate differential responses to chemotherapy. Our goal is to study colorectal cancer at the single-cell level, by doing so we can begin to understand what makes certain cells so aggressive. The ultimate goal is to devise therapies directed at these specific cells.”

Being part of a TFRI Program Project Grant (PPG) has given Dr. O’Brien many new opportunities to work with a wider research community. For example, she will track the growth of different cancer cells using a bar-coding method developed by fellow TFRI researcher Dr. Jason Moffat (University of Toronto).

“TFRI is unique within Canada, and working within the PPG is an incredible opportunity for me. The other investigators are all world-class researchers. I wouldn’t have the opportunity to interact with them otherwise. I can discuss my work and get their input and learn from their different areas of research.”

TFF PPG Principal Investigator Dr. Sean Egan, University of Toronto, says “Dr. O’Brien's proposed work is particularly exciting; by studying cell composition before and after treatment she will be able to answer questions regarding how colorectal cancers respond to both standard chemotherapeutic agents and stem cell-targeted therapies.”

 

Dr. Francis Rodier
Centre de recherche du Centre hospitalier de l’université de Montréal (CRCHUM)

Project Title: Understanding the Impact of Cancer Cell Fate Decisions During Ovarian Cancer Treatment
Award: $450,000
Mentoring Program: TFRI’s Translational Cancer Research Project: A Pan-Canadian Platform for the Development of Biomarker-Driven, Subtype-Specific Management of Ovarian Carcinoma (COEUR)
Mentors/PIs: Dr. Anne-Marie Mes-Masson, Dr. David Huntsman and Dr. Diane Provencher

Dr. Francis Rodier, an associate professor of molecular and cell biology at the department of radiology, radio-oncology and nuclear medicine at the University of Montreal, is studying how ovarian cancer cells respond to the damage caused by radiotherapy and chemotherapy.

In response to treatment, damaged cells have many options; they can repair themselves, they can die, or they can enter a state of permanent growth arrest called “senescence”. Dr. Rodier is particularly interested in this process of senescence, where cells stop growing but don’t die.

“Nobody really knows what is going on inside tumours during treatment. We know if a tumour is regressing or not, but we don’t really understand what’s going on inside,” explains Dr. Rodier. “By analyzing tissue samples from patients pre- and post-treatment, we can characterize different cancer cell responses to therapy and whether senescence has an impact on treatment success and patient survival.”

Dr. Rodier is now mentored by TFRI’s Translational Cancer Research Project, led by Drs. Anne-Marie Mes-Masson and Diane Provencher, at the Centre de recherche du Centre hospitalier de l’université de Montréal (CRCHUM), and Dr. David Huntsman (BC Cancer Agency). Using the COEUR project’s biobank of tissue samples, his initial goal is to determine how much senescence occurs within cancer cells in response to treatment and to identify some biomarkers that could label this process. Any biomarkers found could potentially be used to follow-up treatment evolution in real time or even predict how well a patient will respond to a given treatment.

“Being part of the TFRI network is a huge advantage. It allows me an opportunity to collaborate with other established Canadian researchers that I wouldn’t otherwise have had. I am trying to focus more and more on applying my research to the patient. Learning from Anne-Marie, David and Diane is incredibly important as my background is in a completely different type of science,” says Dr. Rodier.

TFRI project co-leader Dr. Anne-Marie Mes-Masson, director of cancer research at CRCHUM, is delighted that Dr. Rodier has taken an interest in ovarian cancer. “Our CRCHUM biobank has a rich resource in terms of cell lines, cultures, and tumour samples, and Francis’s research will make excellent use of this data.”

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