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    by TFRI Editor | Sep 06, 2016

    TFRI-funded team building on decades of research to overcome treatment failure in lymphoid cancers

    TFRI’s prolific lymphoid cancer team began their research with a simple question: “Why do two-thirds of lymphoma patients recover, while the remainder does not?”

     A decade later their work is being renewed as they continue their mission to find solutions to this problem so all patients diagnosed with lymphoid cancer have better outcomes.

     “We have two major goals in this project: one is generating biomarkers and clinical tests, and the other is to generate novel therapeutics. The main theme is to treat patients more effectively.” says Dr. Christian Steidl, who is co-leading the project with Dr. Joseph Connors. Both are both based at the BC Cancer Agency Centre for Lymphoid Cancer in Vancouver, BC.

     Around 7,680 Canadians are diagnosed with lymphoma each year, making it one of the top five most common cancers in the country. While 60 to 70 per cent of patients are cured with standard therapy, the remainder are not – and it is unclear why.

     The renewed PPG will focus on innovation and technology, as well as expanding the research from diffused large B-cell lymphoma and follicular lymphoma to include both mantle cell and Hodgkin’s lymphoma.

     The project’s four sub-projects plan to conquer some of the biggest challenges in lymphoid cancer research, such as manipulating the tumour microenvironment to make it less hospitable to cancer cells, and preventing patient relapse.

     Lymphoid cancer cells are heterogeneous and constantly evolving, which makes them tough to target with current therapies, says Dr. Steidl. Cutting-edge technology from Vancouver’s Genome Sciences Centre – including mass spectrometry – will be employed to overcome these obstacles.

     The team’s renewal comes on the heels of a successful track record of translation and genomics discovery. Previous achievements include the discovery of recurrent gene mutations and related drug trial design (e.g.tazemetostat) for Non-Hodgkin lymphoma, major influences on treatment policies and education of health care professionals by implementation of a British Columbia-wide system to deliver lymphoma care, as well as biomarker development and implementation of routine-diagnostic tests for inclusion in ongoing clinical trials.

     “We are quite proud about the novelty and innovation that we have produced,” says Dr. Steidl. “We’re very excited about the fact that we have the expertise and the technology in place to tackle the most pressing problems in lymphoma research and patient care.”

    Project Title: Overcoming treatment failure in lymphoid cancer
    Project Leader: Dr. Joseph Connors, BC Cancer Agency Centre for Lymphoid Cancer
    Investigators: Drs. Christian Steidl, Marco Marra, David Scott, Andrew Weng UBC), Gregg Morin, Andrew Mungall, Graham Slack, Sohrab Shah (UBC), Carl Hansen (UBC), Ryan Morin (SFU).
    Award total: $7.5M
    Duration: 2016-2021

    Previously Funded Project: The Terry Fox New Frontiers Program Project Grant in Molecular Correlates of Treatmen Failure in Lymphoid Cancers

    Related Patient Stories: 

    Jackie Ellis: http://www.tfri.ca/en/OurWork/patient-stories/blood-cancers/jackie-ellis

    Darrin Park: http://www.tfri.ca/en/OurWork/patient-stories/blood-cancers/darrin-park

    Adam Green: http://www.tfri.ca/en/OurWork/patient-stories/blood-cancers/adam-green


    by TFRI Editor | Sep 02, 2016

    New Pan-Canadian immunotherapy project aims for greater "hope and options" for women with ovarian cancer

     Dr. O'Hashi lab shot2

    Dr. Pamela Ohashi

    Both around the world and in Canada, teams of researchers are working hard to harness the power of a patient’s own immune system to eradicate cancer through immunotherapy. Hailed now as the fourth arm of treatment, a newly funded TFRI pan-Canadian research team hopes this promising approach will give new hope and options to patients who need it the most.

    “We want to cure cancer and provide new treatment options for Canadians. Our initial focus will be high-grade serous ovarian cancer, a challenging disease in urgent need of new therapies,” explains project leader Dr. Pamela Ohashi, based at the University Health Network’s Princess Margaret Cancer Centre in Toronto.

    High-grade serous cancer (HGSC) is the most common – and fatal – subtype of the disease, comprising around 70 per cent of cases. Prognosis is grim: the five-year survival rate for women presenting with advanced stage disease is less than 30 per cent.

    But it’s not all doom and gloom; this cancer is also known to be “immunogenic,” which means that the cancer can elicit an immune response and, therefore, patients may respond well to immunotherapy.

    "The immunoTherapy NeTwork (iTNT) brings together a team from across Canada who are experts in many different areas such as immunology and genomics,” says Dr. Ohashi, noting the team is also working with Dr. Mathieu Lupien’s new TFRI-funded triple negative breast cancer project. “Our goal is to understand the disease, and to come up with cutting-edge clinical trials so that Canadians have more treatment options by having the opportunity to participate in clinical trials.”

    The group intends to launch a PD-1 checkpoint blockade clinical trial in its first year, and continue to create high-quality information, knowledge and ideas to fuel clinical trials beyond the program’s timeframe during the next four years of funding.

    The team will use state-of-the art immunological, proteomic, bioinformatic and genomic approaches to explore changes in the immune response and tumour microenvironment as patients undergo standard treatments and novel immunotherapies.

    Collaboration between centres and researchers across Canada will greatly benefit iTNT. For example, Dr. Anne-Marie Mes-Masson (Centre de recherche du Centre hospitalier de l’Université de Montréal), co-principal investigator for TFRI’s pan-Canadian Ovarian Experimental Unified Resource (COEUR), will provide access to more than 2,000 ovarian cancer samples to iTNT through the COEUR biobank.  

    It’s really this collection of expertise all focused on one disease that I think is really going to be the power of this network,” says Dr. Ohashi. “It’s all about giving hope and options to cancer patients, and hopefully impacting their survival.”

    Known as The Immunotherapy Network, the team will consist of principal investigators from UHN’s PMCC, the Institute du Cancer de Montreal, CRCHUM, BC Cancer Agency as well as working group members and collaborators from elsewhere in Quebec, Ontario, Alberta, British Columbia, and the US.

    Dr. Brad Nelson, based at the BC Cancer Agency’s Deeley Cancer Centre in Victoria, is the project co-leader and will lead work that will be aimed at providing subtype-specific immunotherapy for patients with HGSC. 

    Dr. Nelson-Deeley lab
    Dr. Brad Nelson (right) project co-leader with members of his team at the Deeley Cancer Centre in Victoria.

    Project Title: 
    The Immunotherapy Network (iTNT): Targeting Ovarian Cancer
    Project Leader: Dr. Pam Ohashi, UHN
    Dr. Brad Nelson (co-leader), BCCA, Hal Berman, PMCC; Marcus Butler, PMCC; Jean-Francois Cailhier, CRCHUM, Benjamin Haibe-Kains, PMCC; Naoto Hirano, PMCC; Rob Holt, BC Cancer Agency; Rejean Lapointe, CRCHUM; Claude Perreault, IRIC; Trevor Pugh, PMCC; Lillian Siu, PMCC: John Stagg, CRCHUM.   
    Award Total: $5.41M 
    Duration: 2016-2012


    New Pan-Canadian immunotherapy project aims for greater “hope and options” to women with ovarian cancer


    New Pan-Canadian immunotherapy project aims for greater “hope and options” to women with ovarian cancer



    by TFRI Editor | Sep 02, 2016

    New TFRI “dream” team will study relapsed brain cancer tumours to find new treatment options 

    Dr. Singh, McMaster University

    A newly funded TFRI “dream team” plans to tackle the most lethal and aggressive brain tumour that occurs in adults by focusing not on the original tumour, but on the relapsed cancer.

    “What we’ve learned so far about glioblastoma is that it always comes back, and when it does come back it’s an entirely different tumour landscape than the original cancer,” says principal investigator and pediatric neurosurgeon Dr. Sheila Singh (McMaster University). “We think it’s so much more valuable to study the disease that’s actually killing the patients and to try to develop targeted therapies against that.”

    Approximately two to three people per 100,000 are diagnosed with glioblastoma each year. Fewer than five per cent of these patients survive beyond five years, with average survival time being around 15 months. (Editor’s note: This form of brain cancer is the same that Tragically Hip band member Gord Downie announced in May that he has.)

    “This is a very horrible and aggressive tumour because it robs people not only of their survival, but also of their quality of life,” says Dr. Singh, noting that she has assembled a “dream team” of scientists to help combat this deadly disease.

    The new PPG is comprised of three complimentary sub-projects led by Dr. Singh, as well as Drs. Sachdev Sidhu, Robert Rottapel and Jason Moffat, both based at the Donnelly Centre For Cellular and Biomolecular Research at the University of Toronto. One team is focused on characterizing the genomic landscape of recurrent glioblastoma using cutting-edge technology such as CRISPR-Cas9 (a genome editing tool recently celebrated as the discovery of the year). The second will design novel immunotherapies and antibodies that can bind to cancer cell receptors and ultimately kill them, and the third will test these new therapies in advanced mice models of glioblastoma. 

    “Our main goal is to get new therapies into patients as soon as possible,” says Dr. Singh, noting that it is her own patients who will be directly benefitting from new brain cancer therapies. “Our team also has the ability to commercialize, to bring industry partners in and help us actually develop drugs based on the antibodies we design…We are the whole package.”

    The complexity of glioblastoma poses a huge challenge, but Dr. Singh says the team is going in “with eyes open” to give back to the community.

    “We’ve got a lot of energy and enthusiasm and we’re going to channel it all into the science,” says Dr. Singh. “To be awarded this team grant and to function as a leader has been one of the most incredible honours of my life.”

    A former TFRI New Investigator, Dr. Singh has been involved in TFRI’s pan-Canadian translational glioblastoma project which is led by Dr. Greg Cairncross, University of Calgary, and involves a team of investigators based at research centres across the country. The latter project is also focused on bringing new treatments to the clinic for these patients, including one currently being tested in a clinical trial launched in spring 2016.

    Project TitleTargeting clonal heterogeneity in treatment-refractory glioblastoma with novel and empiric immunotherapies 
    Project Leader: Dr. Sheila Singh, McMaster University
    Investigators: Drs. Dachdev Sidhu and Jason Moffatt, Donnelly Centre for Cellular Biomolecular Research, University of Toronto; Dr. Robert Rottapel, Princess Margaret Cancer Centre, UHN and U of T. 
    Award Total: 2.25 M
    Duration: 2016-2019

    Related Patient Story:

    Adam Coules: http://www.tfri.ca/en/OurWork/patient-stories/brain-cancer/adam-coules

  • “Smart” nanoparticle (PEARLs) a promising gem to target and treat tumours with greater precision

    by User Not Found | Jul 14, 2016

    Dr. Zheng
    Dr. Gang Zheng

    Canada – July, 14, 2016 – Dr. Gang Zheng and a team of biomedical researchers have discovered a “smart” organic, biodegradable nanoparticle that uses heat and light in a controlled manner to potentially target and ablate tumours with greater precision.

    The proof-of-concept findings, published online today and designated a “very important paper” in the leading chemistry journal Angewandte Chemie, provide a viable approach to boosting the clinical utility of photo-thermal therapy in treating cancer, says Dr. Zheng, senior scientist at the Princess Margaret Cancer Centre and professor of medical biophysics at the University of Toronto. Dr. Zheng also holds the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research. He talks about and demonstrates the research at https://youtu.be/EEN6Mz5iWBI.

    In the lab, using phantom models, the “smart” nanoparticle the team has dubbed  PEARLs – photo-thermal enhancing auto-regulating liposomes – showed how it can solve the two bottlenecks currently preventing more effective use of photo-thermal therapy with patients. These are overheating of tissue that can cause collateral damage during treatment, and the inability to ablate larger tumour volumes because the light stops travelling when it is absorbed.

    Explains the chemist: “Our smart nanoparticle is super cool. It can absorb light, generate heat and ablate the tumour. It’s a thermal sensor and once it reaches the desired ablation temperature of 55C, it becomes invisible, allowing the light to move deeper into more areas of the tumour and repeat the treatment process.

    “The result is a promising new way to heat and ablate larger volumes of the tumour with minimal damage to surrounding tissues in a controlled and precise way. The next step is to conduct pre-clinical studies to test the concept further.”

    For the past 10 years at PMCC, Dr. Zheng’s research has focused on advancing nanoparticle technology by harnessing light, heat and sound to advance tumour imaging and targeted treatment.

    Study: Controlling Spatial Heat and Light Distribution by Using Photothermal Enhancing Auto-Regulated Liposomes (PEARLs)

    Kenneth K Ng. Robert A. Weersink, Liang Lim, Brian C. Wilson, Gang Zheng 

    The research was funded by the Terry Fox Research Institute, Prostate Cancer Canada, the Canadian Institutes of Health Research, Ontario Institute for Cancer Research, the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, the Tanenbaum Chair in Prostate Cancer Research, and The Princess Margaret Cancer Foundation. 

    TFRI Links, Fall 2016
  • Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood

    by User Not Found | Jul 14, 2016

    AML cells

    Canada – July 14, 2016) – International stem cell scientists, co-led in Canada by Terry Fox-funded scientist Dr. John Dick and in the Netherlands by Dr. Gerald de Haan, have discovered the switch to harness the power of cord blood and potentially increase the supply of stem cells for cancer patients needing transplantation therapy to fight their disease.

    The proof-of-concept findings, published online today in Cell Stem Cell (http://dx.doi.org/10.1016/j.stem.2016.06.008) provide a viable new approach to making more stem cells from cord blood, which is available through public cord blood banking, says co-principal investigator John Dick, senior scientist, Princess Margaret Cancer Centre, University Health Network (UHN). Dr. Dick is also professor, Department of Molecular Genetics, University of Toronto, and holds a Canada Research Chair in Stem Cell Biology. The co-principal investigator was stem cell scientist Gerald de Haan, scientific co-director, European Institute for the Biology of Ageing, University Medical Centre Groningen, the Netherlands.  Dr. Dick talks about their joint research at https://youtu.be/cpEmKnjkb9s.

    “Stem cells are rare in cord blood and often there are not enough present in a typical collection to be useful for human transplantation. The goal is to find ways to make more of them and enable more patients to make use of blood stem cell therapy,” says Dr. Dick. “Our discovery shows a method that could be harnessed over the long term into a clinical therapy and we could take advantage of cord blood being collected in various public banks that are now growing across the country.”

    Currently, patients needing stem cell transplants are matched to an adult donor with a compatible immune system through international registry services. But worldwide, many thousands of patients are unable to get stem cell transplants needed to combat blood cancers such as leukemia because there is no donor match.

    “About 40,000 people receive stem cell transplants each year, but that represents only about one-third of the patients who require this therapy,” says Dr. Dick. “That’s why there is a big push in research to explore cord blood as a source because it is readily available and increases the opportunity to find tissue matches. The key is to expand stem cells from cord blood to make many more samples available to meet this need. And we’re making progress.”

    Although there is much research into expanding the rare stem cells present in cord blood, the Dick-de Haan teams took a different approach. When a stem cell divides it makes a lot of progenitor cells immediately downstream that retain key properties of being able to develop into everyone of the 10 mature blood cell types, but they have lost the critical ability to self-renew (keeping on replenishing the stem cell pool) that all true stem cells possess.

    In the lab, analysing murine and human models of blood development, the teams discovered that microRNA (mirR-125a) is a genetic switch that is normally on in stem cells and controls self-renewal; this normally gets turned off in the progenitor cells.

    “Our work shows that if we artificially throw the switch on in those downstream cells, we can endow them with stemness and they basically become stem cells and can be maintained over the long term,” says Dr. Dick.

    In 2011, Dr. Dick isolated a human blood stem cell in its purest form – as a single stem cell capable of regenerating the entire blood system, providing a more detailed road map of the human blood development system, and opening the door to capturing the power of these life-producing cells to treat cancer and other debilitating diseases more effectively.

    Dr. Dick is also senior scientist at the McEwen Centre for Regenerative Medicine (UHN) and director of the Cancer Stem Cell Program at the Ontario Institute for Cancer Research.

    StudyEctopic miR-125a expression induces long-term repopulating stem cell capacity in mouse and human hematopoietic progenitors

    Authors: Edyta E. Wojtowicz, Eric R. Lechman, Karin G. Hermans, Erwin M. Schoof, Erno Wienholds, Ruth Isserlin, Peter A. van Veelen, Mathilde J.C. Broekhuis, George M.C. Janssen, Aaron Trotman-Grant, Stephanie M. Dobson,Gabriela Krivdova, Jantje Elzinga, James Kennedy, Olga I. Gan, Ankit Sinha,Vladimir Ignatchenko, Thomas Kislinger, Bertien Dethmers-Ausema,Ellen Weersing, Mir Farshid Alemdehy,Hans W.J. de Looper, Gary D. Bader, Martha Ritsema, Stefan J. Erkeland, Leonid V. Bystrykh,John E. Dick,and Gerald de Haan

    Funding: The Canadian team’s research published today was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Terry Fox Foundation, the Ontario Institute for Cancer Research, the Canada Research Chair in Stem Cell Biology, The Princess Margaret Cancer Foundation, and the Ontario Ministry of Health and Long-term Care.

    TFRI Links, Fall 2016
  • Study by TFRI-funded team underscores importance of accurate diagnosis for rare ovarian and other cancers

    by User Not Found | Jun 14, 2016

    David Huntsman Melissa McConechy Dr. David Huntsman with Dr. Melissa McConechy, first author of the published JNCI paper

    Terry Fox-funded cancer researchers in BC led an international study to develop a new method to improve diagnosis of a rare sub-type of ovarian cancer that has been notoriously difficult to accurately identify. The team has created an algorithm to diagnose and predict the clinical course of granulosa cell cancers of the ovary.

    “Effective cancer treatments rely on having an accurate diagnosis in the first place, and the results of our research underline the importance of this,” says lead investigator Dr. David Huntsman, the Dr. Chew Wei Memorial Professor of Gynecologic Oncology at the University of British Columbia and scientific leader of OVCARE, British Columbia’s multidisciplinary ovarian cancer research program.

    Outcomes for adult-type granulosa cell tumours (AGCTs), which make up 3-5% of ovarian cancers, seemed to be all over the place. While standard diagnosis of AGCT is based on how tumour tissue appears under a microscope, recent research found that many AGCTs had a mutation in the FOXL2 gene. The Vancouver-based team wanted to study this genetic aspect in more detail to see if FOXL2 could be used as a robust marker for the disease.

    For their study, the group used historical cases of tumours categorized as AGCT of the ovary from three major European centres.  “While the cases we examined had the most accurate diagnosis possible at the time, our team found that about 20 per cent were actually of different sub-types of ovarian cancer. By assessing only the true cases of AGCT, a clearer picture emerged: the survival rates were very high for those with true AGCT and more than 95 per cent of those cases had a mutation in the FOXL2 gene, making it a disease defining marker to use in diagnosis,” explains Dr. Huntsman.

    The majority of deaths attributed to AGCT in the study were actually caused by aggressive forms of other types of ovarian cancer, says Dr. Huntsman, head of TFRI’s New Frontiers Program Project Grant in the Genomics of Forme Fruste Tumours. The project studies rare tumours; historically, research on these kinds of tumours has yielded knowledge on our understanding of common cancers.

    Dr. Huntsman says their research produced other important information for patients and doctors.  “For those with true AGCT we realize that the prognosis is actually very good, removing a great deal of stress for patients and their families. For those who might have previously been diagnosed with AGCT, but who actually have a different form of ovarian cancer, this method will prompt clinicians to follow-up with further tests for an accurate diagnosis and ensure a more appropriate treatment plan. We wrote the paper with future patients in mind and hope it will be used by health care providers to help explain the implications of this diagnosis and in many cases mitigate the fear that comes with a cancer diagnosis.”

    The research paper was published online in June 2016 in the Journal of the National Cancer Institute.

    More information

    The Terry Fox New Frontiers Program Project Grant in the Genomics of Forme Fruste Tumours has been funded by the Terry Fox Research Institute since 2010. Forme Fruste tumours are rare and unusual tumours that can pose a huge challenge to clinicians due to the low prevalence of each individual disease. Historically, research on rare cancers has directly impacted the way more common cancers have been studied and understood.

    About TFRI
    Launched in October 2007, The Terry Fox Research Institute is the brainchild of The Terry Fox Foundation and today functions as its research arm. TFRI seeks to improve significantly the outcomes of cancer research for the patient through a highly collaborative, team-oriented, milestone-based approach to research that will enable discoveries to translate quickly into practical solutions for cancer patients worldwide. TFRI collaborates with over 70 cancer hospitals and research organizations across Canada. TFRI headquarters are in Vancouver, BC. www.tfri.ca

    About OVCARE
    OVCARE (www.ovcare.ca) is British Columbia’s multidisciplinary and  multi-institutional ovarian cancer research team. OVCARE operations including the work described in this manuscript are performed at the BC Cancer Agency and the Vancouver General Hospital. In addition to peer reviewed funding from TFRI and other agencies, OVCARE is generously supported by the BC Cancer Foundation, the Vancouver General Hospital and UBC Hospital Foundation and UBC Faculty of Medicine. 

  • Terry Fox researcher leads international conference on ‘devastating’ cancer predisposition syndrome

    by User Not Found | Jun 03, 2016

    Terry Fox-funded researcher Dr. David Malkin, The Hospital for Sick Kids, Toronto, Ontario, was in Columbus, Ohio this week to co-lead the 2016 International Li-Fraumeni Syndrome (LFS) Conference. TFRI funds two projects led by Dr. Malkin, including one focusing solely on LFS.

    LFS is caused by inherited mutations in a gene called TP53, one of the most frequently mutated genes in human cancers, affecting around one in 1,000 to 5,000 people. The TP53 gene plays a significant role in suppressing tumour growth, which is compromised in people with LFS, thus increasing their risk of developing many cancers at an early age.

    Patients have an almost 100 per cent chance of developing cancer in their lifetime – in any body part and at any age – and treatment options are limited.

    “The challenges faced by these children and [their] families are devastating,” said Dr. Malkin. “It’s like a ticking time bomb waiting for the next cancer to develop, and we don’t clearly have any effective ways to treat LFS any different than how we treat any other cancer.”

    More than 200 people attended the conference, which was hosted by the Li-Fraumeni Syndrome Association (LFSA). Around half of the participants were leading researchers, clinicians, and genetic counsellors from around the world; the remainder were families affected by the devastating disease – with some coming from as far away as Brazil and New Zealand.

    “This is an amazing opportunity to collaborate and combine worlds to try and figure this disease out,” said Dr. Malkin at the conference’s opening. “We will get the answers by blending the two worlds and working together – and only by working together.”

    Other conference partners included Soccer for Hope, Nationwide Children’s Hospital, and The Ohio State University.

  • ASM photos now online

    by User Not Found | May 13, 2016
    More than 200 Terry Fox researchers attended the 7th Annual Scientific Meeting in Vancouver last week. Under the theme "Understanding Cancer Over Time and Space", the plenary sessions triggered some engaging discussion among attendees and the rapid fire poster talks introduced many trainees to the Terry Fox research family. Photos from the event are now online.
  • TFRI is now smartphone friendly

    by User Not Found | Apr 28, 2016

    Visitors to our site who use mobile or tablet devices will see some welcome updates today as tfri.ca has had a mobile-friendly upgrade. When you visit our website on a mobile device you will find a menu and navigation modified for smaller screens, helping you find the information you need quickly and easily. We hope you continue to enjoy TFRI content no matter what device you use.

    A screenshot showing tfri.ca as seen on a smartphone

  • Dr. Victor Ling receives lifetime achievement award

    by User Not Found | Apr 22, 2016

    Victor Ling BC LifeSciences AwardCongratulations to Dr. Victor Ling, TFRI's President and Scientific Director, who has been honoured with the LifeSciences BC Dr. Don Rix Award for Lifetime Achievement. The award celebrates Dr. Ling's many contributions to cancer research during his long career. Dr. Ling is an authority on multi-drug resistance in cancer, and is well-known for his discovery of P-glycoprotein, the first molecule identified to be responsible for drug resistance. Congratulations to Dr. Ling as he continues to move cancer research forward through his leadership at TFRI.

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