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  • Study finds mitochondrial mutations drive prostate cancer aggression

    by TFRI Admin | Feb 15, 2018

    F0202638-Prostate_cancer_cells,_illustration-SPL

    While nuclear mutations are widely acknowledged as a driver of cancer tumours, the role of maternally inherited mitochondrial genome mutations has not been extensively explored – but now a paper from a prolific TFRI-funded team has suggested an important interplay between the two mutations when it comes to prostate cancer tumours.

    The study was recently published in Nature Communications and spearheaded by Drs. Julia Hopkins, Paul Boutros (Ontario Institute for Cancer Research) and Dr. Robert Bristow (formerly with Princess Margaret Cancer Centre). The human genome consists of two genomes – the nuclear and mitochondria – although the nuclear genome is the predominant focus in most cancer research. The present study took a unique approach, analyzing the mitochondrial genomes of 384 localized prostate tumours and identifying numerous mitochondrial single-nucleotide variants (mtSNVs).

    The results were significant: the mitochondrial genomes of prostate cancer patients showed the potential for nuclear variants to interact with mitochondrial variants in a form of “cross-talk”. Mitochondrial mutations displayed a complicated interplay with nuclear mutational characteristics, and the two appear to work together to determine and drive tumour aggression.

    The team also found a link between mitochondrial mutations and biochemical relapse, and patients with both mutations in a specific non-coding region of the mitochondrial DNA and MYC copy number aberrations appear to have worse outcomes than those without. Further, older patients had more mtSNVs compared to those diagnosed at a younger age, a finding the researchers intend to investigate more.

    Proteins encoded in the mitochondrial genome are all part of the Oxidative phosphorylation pathwayand mutations in these genes can affect mitochondrial function, which has been shown to be essential for tumour development. Given this, the team believes it is important to identify any mutations in the mitochondrial genome, as well as to include its analysis in whole genome studies. The study suggests the addition of mtSNVs to prognostic biomarkers may be an effective way of improving prediction of patient outcome, supporting triage of patients with low-risk disease to surveillance protocols and with high-risk disease to adjuvant therapy regimens.

    Prostate cancer is the third leading cause of cancer-related death in Canadian men. Some types are aggressive and lethal, requiring aggressive treatment, while others are considered indolent and treatment may not be needed. These study findings can be used as a resource for future work in prostate cancer. It also underscores the importance of including the mitochondrial genome in future genomic analysis studies.

    Study: Mitochondrial mutations drive prostate cancer aggression

    Authors: Julia F Hopkins, Veronica Y Sabelnykova, Joachim Weischenfeldt, Ronald Simon, Jennifer A Aguiar, Rached Alkallas, Lawrence E Heisler, Junyan Zhang, John D Watson, Melvin LK Chua, Michael Fraser, Francesco Favero, Chris Lawerenz, Christoph Plass, Guido Sauter, John D McPherson, Theodorus van der Kwast, Jan Korbel, Thorsten Schlomm, Robert G Bristow & Paul C Boutros

    Funding: This project was supported in part by a Terry Fox Research Institute New Investigator Award to Paul C. Boutros.

  • 2017 Marathon of Hope Lecture Series

    by TFRI Editor | Feb 08, 2018
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    As part of its 10th anniversary celebration, TFRI presented a session titled The Marathon of Hope Lecture Series at the Canadian Cancer Research Conference(Vancouver) in November 2017 that featured four premier TFRI-funded researchers: John Dick (PM, Toronto), John Bell (OHRI, Ottawa), Stephen Lam (UBC, Vancouver) and Marco Marra, BC Cancer .
    We asked teach to speak on their vision of how their research may transform outcomes for cancer patients and bring us closer to achieving Terry's dream. The session was introduced by TFRI President Dr. Victor Ling and each speaker gave a 20-minute talk. We are pleased to present videos of all of the talks here, featuring slides presented. 
    We hope you enjoy these talks as much as those in attendance did!

    John Dick: Is stemness the biomarker and therapeutic target we have been missing?

    John Bell: Using viruses to stimulate the body's fight against cancer cells

    Stephen Lam; Lung cancer screening: Opportunity to improve health care delivery

    Marco Marra: Genomic approaches to cancer outcomes

  • 2017 TFRI Ontario Node Day Photos

    by TFRI Admin | Jan 19, 2018
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    The annual Terry Fox Research Institute’s Ontario Node Research Symposiumhosted by Drs. Marianne Koritzinsky, Trevor Shepherd, Sheila Singh and Robert Rottapel, took place Monday, Dec. 4, 2017 at the  MaRS Discovery Centre in Toronto. More than 200 people from across the province attended the event, entitled "Deconstructing and Reconstructing Tumour Complexity." 

    Check out photos from the event here



  • New study shows viruses and checkpoint inhibitors work together to cure resistant breast cancer in mice

    by TFRI Admin | Jan 03, 2018


    Drs. Marie-Claude Bourgeois-Daigneault and John Bell. 

    Immunotherapy, which helps the body’s immune system attack cancer, has revolutionized treatment for cancers such as melanoma and leukemia. However, many other kinds of cancer remain resistant. 

    A new study led by researchers at The Ottawa Hospital (TOH) and the University of Ottawa suggests that a combination of two immunotherapies (oncolytic viruses and checkpoint inhibitors) could be much more successful in treating breast cancer and possibly other cancers. The study, by members of  Dr. John Bell's lab in Ottawa, was funded by TFRI and other Canadian research partners and appears in Science Translational Medicine

    “It was absolutely amazing to see that we could cure cancer in most of our mice, even in models that are normally very resistant to immunotherapy,” said Dr. Marie-Claude Bourgeois-Daigneault, lead author of the study and a postdoctoral fellow. The work was conducted in mouse models.  “We believe that the same mechanisms are at work in human cancers, but further research is needed to test this kind of therapy in humans,” she said in a TOH press release dated Jan 3.

    In the current study, the researchers focused on “triple negative” breast cancer, which is the most aggressive and difficult-to-treat kind of breast cancer.The researchers studied three mouse models of triple-negative breast cancer, and found that all were resistant to a checkpoint inhibitor which is commonly used to treat other kinds of cancer. They also found that while an oncolytic virus called Maraba could replicate inside these cancers and help the mouse’s immune system recognize and attack the cancer, the virus alone had minimal impact on overall survival.

    The researchers then tested the virus and checkpoint inhibitor together in models that mimic the metastatic spread of breast cancer after surgery, which is very common in patients. They found that this combination cured 60 to 90 per cent of the mice, compared to zero for the checkpoint inhibitor alone and 20 to 30 per cent for the virus alone. In these models, the virus was given before the surgery and the checkpoint inhibitor was given after.

    “Our immune system is constantly trying to recognize and kill cancer cells, but the cancer cells are always trying to hide from it,” explained Dr. Bell, a senior scientist and project leader of TFRI's Program Project Grant on the Canadian Oncolytic Virus Consortium. “When you infect a cancer cell with a virus, it raises a big red flag, which helps the immune system recognize and attack the cancer. But in some kinds of cancer this still isn’t enough. We found that when you add a checkpoint inhibitor after the virus, this releases all the alarms and the immune system sends in the full army against the cancer.”

    A recently published clinical trial confirmed that oncolytic viruses and checkpoint inhibitors have potential for treating melanoma, but this is the first study to show the potential in breast cancer. It is also the first study to test viruses and checkpoint inhibitors in a surgery and metastasis model, which is particularly relevant for patients.

    Ongoing clinical trials are testing oncolytic viruses (including Maraba) in combination with checkpoint inhibitors in people with cancer. 

    The Maraba virus therapy was jointly pioneered by Dr. John Bell (The Ottawa Hospital, University of Ottawa), Dr. David Stojdl (Children’s Hospital of Eastern Ontario, University of Ottawa) and Dr. Brian Lichty (McMaster University), all members of the long-funded COVCo team.

    The research described here was published in Science Translational Medicine on January 3, 2018. The publication is titled “Neo-Adjuvant Oncolytic Virotherapy Before Surgery Sensitizes Triple-Negative Breast Cancer to Immune Checkpoint Therapy”.

     

  • The Potential of Precision Medicine: TFRI's 2017 ASM Photos Now Online

    by TFRI Admin | Dec 12, 2017
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    More than 200 cancer researchers attended TFRI's 8th Annual Scientific Meeting in Vancouver on Nov. 4. Under the theme "The Potential of Precision Medicine", the plenary sessions triggered some engaging discussion among attendees and the rapid fire poster talks introduced many trainees to the Terry Fox research family.

    Click here to see a selection of photos taken at the event.  

  • Milestone Videos: TFRI Celebrates 10th Anniversary

    by TFRI Admin | Dec 07, 2017

    This was a big year for the Terry Fox Research Institute: 2017 marked our 10th anniversary. Here are two videos we created to celebrate this milestone, telling the story of TFRI's origins, and how we are achieving Terry Fox's dream of finding cures for cancer through research. 

    Check out photos from the 10th anniversary here.

     

  • Canadian pediatric researchers, funders join forces, commit $16.4M to give young people across the country a fighting chance against cancer

    by TFRI Admin | Nov 24, 2017

    PROFYLE Group Shot
    ​(Photos: The Hospital for Sick Children)


    FOR THE FIRST TIME IN CANADIAN HISTORY, more than 30 pediatric cancer research and funding organizations have joined forces through Terry Fox PROFYLE, a pan-Canadian project to give children, adolescents and young adults who are out of conventional treatment options another chance to beat their cancer. The project was announced Nov.23 at The Hospital for Sick Children in Toronto. 

    Short for PRecision Oncology For Young peopLE, the Terry Fox Research Institute (TFRI) and these research and funding partners are working and fundraising together under a unique partnership that to date is providing a total of $16.4 million to molecularly profile the tumours of these patients, no matter where they live in Canada. For example, if Terry Fox had been diagnosed with cancer today, he would have been eligible for PROFYLE when the tumour returned and spread to his lungs.


     A $5-million investment by TFRI is the catalyst bringing together top scientists and clinicians, research centres, cancer charities and foundations at children’s hospitals across the country to create new hope for young people who need it the most.

    Marlow, Mike and TanyaEight-year-old Marlow Ploughman is one of these children. When her late-stage rhabdomyosarcoma (muscle cancer) relapsed for the fourth time, doctors told Marlow’s parents there were no more conventional treatments left to try. The news was devastating – but then the Kingston, Ont. family learned about Terry Fox PROFYLE.

    “[Terry Fox PROFYLE] is extremely important, because with children like Marlow we have very few options except the one conventional protocol that we’re given,” said Marlow’s mom, Tanya Boehm. “PROFYLE provides a key to unlock the door to perhaps more options — or at least provides us more time to wait for some more options to come.”


    While there has been dramatic improvement in treatments and outcomes for many pediatric cancers over the last three decades, for the 20 per cent of young people whose cancers have spread, returned, or are resistant to treatment, outcomes remain grim.

    Project lead Dr. David Malkin, based at The Hospital for Sick Children (SickKids) in Toronto, says PROFYLE is bringing together the entire pediatric and young adult national clinical and research expertise in precision medicine in a way that has never before been done in Canada.

    “One of the big wins for Canada is that instead of working in somewhat independent silos, we have created a massive formulized collaborative and co-operative program to achieve this goal,” said Dr. Malkin. “The second, longer-term hope is that we will have developed a mechanism as we learn more and more about genetics and genomics of cancer, so that every newly diagnosed child, adolescent and young adult will eventually have the genome of their tumour sequenced, to give them more opportunities for therapy and accelerate their return to health.”

     Funding for Terry Fox PROFYLE is expected to grow over the life of the five-year project as new funders join on.

    "We are extremely thrilled the TFRI has been instrumental in bringing these top-tier Canadian cancer researchers and funding partners together for what we believe is one of the most important cancer initiatives in our country. Our sincere thanks to everyone for this formidable, generous collaboration,” said Dr. Victor Ling, TFRI president and scientific director.

    Read about the launch of Terry Fox PROFYLE in the news

  • B.C. Lung Screen Trial recruiting 2,000 people for cancer screening study

    by TFRI Admin | Oct 26, 2017

    The B.C. Lung Screen Trial at Vancouver General Hospital is currently recruiting 2,000 individuals from the Lower Mainland who are between 55 and 80 years of age, with at least a 30-pack-years smoking history to take part in a new lung cancer research project. The study is jointly funded by the VGH-UBC Hospital Foundation, the BC Cancer Foundation, and the Terry Fox Research Institute.

    Lung cancer is the leading cause of cancer deaths in both men and women, and less than 18% of patients survive five years or more. However if lung cancer is diagnosed early (through screening) and treated early before it spreads outside the air passages, over 77% of patients survive five years or more. Low dose computed tomography, often simply called "CT scan", can pick out tiny cancers that are not visible by previous tests.

    Ottawa resident Debi Lascelle took part in the Terry Fox Research Institute study, and credits the early-detection protocol with catching her cancer while it was still curable. 

    “Being involved in this study quite literally saved my life,” said Lascelle, who had a 13-milimetre tumour removed from her right lung through surgery and has been cancer-free ever since. “How do you adequately find a way to say, ‘Thank you for my life’? It’s been seven years and I still haven’t found a way.”

    The B.C. Lung Screen Trial, a study led by Dr. Stephen Lam (Respiratory Medicine), Dr. John Yee (Thoracic Surgery) and Dr. John Mayo (Radiology) at the Vancouver General Hospital in association with the B.C. Cancer Agency, aims to improve lung cancer survival rates by using early detection low dose CT scanning which has been shown to reduce lung cancer mortality by 20% in a larger randomized clinical trial.

    Interested in taking part? Check out the study website or contact: 

    Website: Bclungscreentrial.com

    Email: bclungscreening2015@gmail.com

    Telephone: 1-604-675-8088

     

     

  • Terry Fox research team’s model for detecting lung cancer saves lives, is a world leader: study

    by TFRI Admin | Oct 18, 2017
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    Dr. Stephen Lam discusses lung cancer nodules with study participant Mr. Chris Douglas. Photo credit: Chuck Russell, BC Cancer Agency

    A pan-Canadian team of cancer researchers has developed a predictive model for detecting early-stage lung cancer in high-risk individuals with significantly greater accuracy than other leading models. This Terry Fox Research Institute study suggests the team’s innovative approach could be considered for use in lung cancer screening programs both in Canada and around the world.

    The results, highlighted in a study published in the Oct.18th edition of The Lancet Oncology, were presented at the 18th World Conference on Lung Cancer in Yokohama, Japan on Wednesday by co-principal investigator Dr. Stephen Lam (chair of British Columbia’s Provincial Lung Tumour Group at the BC Cancer Agency and a professor of medicine at the University of British Columbia).

    “We knew our Pan Can Lung Cancer Risk Prediction Model would probably work better than other models, but we were surprised at how much better,” says Dr. Lam. “We have the means to identify high-risk people, and we know we can find cancer early. This model provides a superior tool that would be beneficial in Canada and around the world in saving more lives.”

    The Pan Can Lung Cancer Risk Prediction Model – which is used to determine which individual should undergo annual CT screening to detect early-stage lung cancer – outperformed comparable models such as The National Lung Screening Trial (led by the National Cancer Institute in the US). The Pan Can Model was developed with $8.4-million support from the Terry Fox Research Institute (TFRI), and The Canadian Partnership Against Cancer.

    Ottawa resident Debi Lascelle took part in the Terry Fox Research Institute study, and credits the early-detection protocol with catching her cancer while it was still curable.

    “Being involved in this study quite literally saved my life,” said Lascelle, who had a 13-milimetre tumour removed from her right lung through surgery and has been cancer-free ever since. “How do you adequately find a way to say, ‘Thank you for my life’? It’s been seven years and I still haven’t found a way.”

    The PanCan Model diagnosed lung cancer in 6.5 per cent of people screened with a follow-up of five years, compared to the four per cent of cases found by the National Lung Screening Trial over a longer term (6.5 years). Further, 77 per cent of the lung tumours diagnosed with the Pan Can Model were caught in early-stages when the cancer is potentially curable, compared to 57 per cent in the NLST study. Lung cancer is the most common cause of cancer death around the world – yet if caught early enough it can be cured in 70 per cent of cases, making early detection a critical feature in a predictive model.

    Currently, both the US and Canadian lung cancer screening guidelines are based on age and smoking history. One of the main advantages of the Pan Can Model is it uses a risk prediction tool that looks at numerous additional variables: sex, family history of lung cancer, chronic obstructive pulmonary disease, educational level and body mass index.

    “Looking at just age and smoking history is actually a very inaccurate way of doing things, because we know that age and smoking history alone finds 33 per cent fewer people with lung cancer than the PanCan prediction tool,” adds Dr. Lam.

    The TFRI Pan-Canadian Early Lung Cancer Detection Study was expanded in 2017 to examine factors such as genetics and air pollution in lung cancer risk. The study is looking to recruit 2,000 British Columbians who have smoked for at least 20 years and are between 55 and 80. Dr. Victor Ling, president and scientific director of The Terry Fox Research Institute, says The Lancet Oncology study results epitomize the type of cutting-edge, precision medicine TFRI strives to fund across Canada.

    “The Terry Fox Research Institute is thrilled at the success of the Pan Can Lung Cancer Risk Prediction Model,” remarks Dr. Ling. “The paper’s recommendations have the opportunity to better detect this deadly disease in high-risk individuals. We believe this research holds great promise for providing improved outcomes for lung cancer patients both within Canada and around the world.”

    Original article from The Lancet Oncology: Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study

    Check out The Canadian Press story (shared by CTV News) about the research here


  • Four premier TFRI investigators will present Marathon of Hope talks at CCRC

    by TFRI Editor | Sep 06, 2017

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    (From top left to bottom right: Dr. John Bell, Dr. Stephen Lam, Dr. John Dick, and Dr. Marco Marra).
     

    TFRI is pleased to announce that it will be presenting a concurrent session (D6 in program) at the upcoming Canadian Cancer Research Conference featuring talks by four outstanding Canadian investigators: Dr. John Bell (OHRI) Dr. John Dick (UHN), Dr. Stephen Lam (BC Cancer Agency), and Dr. Marco Marra (BC Cancer Agency). The session is titled the Marathon of Hope Lectures and it will be held on Monday, Nov. 6, 2017 (3-4:30 p.m.). 

    These investigators will share their vision of how their research may transform outcomes for cancer patients and bring us closer to achieving Terry’s dream. Also, Monday morning we will hold our Early Morning Run/Walk to permit  all CCRC attendees to participate and help celebrate Terry’s legacy, Canada’s 150th and our 10th Anniversary. Please mark your calendars for these great events!



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