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  • 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
    TFRI_ASM_4935

    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. 


     

  • 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.

    To learn more about Terry Fox PROFYLE, click here.

    Canadian Press Wire Story: https://www.ctvnews.ca/mobile/health/canadian-initiative-fuelled-by-terry-fox-s-dream-may-be-only-hope-for-young-1.3690808

    Globe and Mail article: https://www.theglobeandmail.com/amp/life/health-and-fitness/health/canada-wide-program-aims-to-get-young-cancer-patients-faster-access-to-new-therapies/article37058522/

  • 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
    tfri_2737
    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

    IMG_5880
    (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!



  • TFRI's 8th ASM focuses on potential of precision medicine

    by TFRI Editor | Sep 06, 2017

    TFRI_ASM_Day2_05

    TFRI’s one-day 8th Annual Scientific Meeting on Saturday, Nov. 4, 2017 in Vancouver will feature talks related to the theme of the potential of precision medicine. There will be three plenaries  on the subjects of cancer biology, prognostic strategies and therapeutic strategies. A fourth plenary will feature concurrent rapid-fire talks by selected trainees who will be presenting abstracts at this year's CCRC meeting (Nov. 5-7th). 

    Among this year’s ASM key speakers are:  Dr. Connie Eaves, BC Cancer Agency; Dr. Ivan Topisirovic, McGill University and Dr. Brian Wilson, UHN, and more than 75 rapid-fire talks are expected. Registration for those invited and confirmed to attend the meeting closes on Thursday, Sept. 21, 2017.

    Visit our ASM site for more information and/or to register.  

    TFRI Links, Summer 2017
  • It’s not too late to join a Terry Fox Run research team!

    by TFRI Editor | Sep 06, 2017

    Dr. Singh team

    The annual Terry Fox Run is just around the corner and our purple-shirted research teams - along with their friends and families - will be out in full force again this year! To date, more than 16 teams have confirmed their participation in the upcoming run on Sunday, Sept. 17th. Many are returning teams from last year!

    Thank you so much for supporting cancer research and Terry’s cause. A special thanks to all our team captains for leading the charge. It’s not to late to join or form a team. Visit the TFF web site to find a team at your institution (select Sponsor a Participant/Search team name TFRI)  or join the TFRI-HQ site led by our captain Dr. Victor Ling.  We are hoping to top last year’s amazing success: TFRI was the top multi-province team last year raising more than $116,000. 

    TFRI Links, Summer 2017
  • Canadian, international researchers find new candidate drivers, subtype diversity in study of whole-genome landscape for children’s brain cancer

    by TFRI Admin | Sep 06, 2017

    IM-0001-0016

    Medulloblastoma is the most common childhood brain cancer, and current treatments often have debilitating effects on developing children – a situation that highlights the need for molecularly targeted treatments with reduced toxicity. The present study analyzed hundreds of sequenced medulloblastoma (MB) samples, identifying numerous new targets that could give children with this disease new, less harmful therapeutic options.

    The research was led by Dr. Michael Taylor (Toronto’s Hospital for Sick Children) and Dr. Peter Lichter (German Cancer Research Center, Heidelberg), and was recently published with first author Dr. Paul. A Northcott (Nature, July 2017).Targeted treatments for MB are limited despite a significant need for new therapies, a dilemma that spurred the team to undergo a deep dive into the full range of genetic lesions and molecular heterogeneity that contribute to the different MB subgroups.

    Previous research from Dr. Taylor’s group showed there are four main molecular subgroups –Wingless (WNT), Sonic hedgehog (SHH), Group 3 and Group 4 – that have distinct epigenetic and transcriptional signatures. In the present study, the team examined 491 sequenced, previously untreated medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analyzed cases.

    The results were impressive: on an individual gene level, new candidate drivers were discovered in each of the different subgroups, and were assigned to most patients belonging to Group 3 and Group 4, greatly enhancing previous knowledge. For example, all 36 WNT MBs sequenced in this study were confidently explained by mutations in at least one or more driver genes, and the team assigned at least one driver gene to more than 95 per cent of patients with SHH MB. Further, new molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and ‘enhancer hijacking’ events that activate PRDM6.

    Applying integrative genomics to a large study of patient samples derived from medulloblastoma revealed a series of cancer genes and biologically relevant subtype diversity, some of which could be targeted with new, personalized therapeutics. The present study’s findings – combined with future research – will likely help to advance treatments and to improve prognosis for children and families affected by this devastating brain cancer.

    Study: The whole-genome landscape of medulloblastoma subtypes

    Authors: Paul A. Northcott Ivo Buchhalter, A. Sorana Morrissy, Volker Hovestadt, Joachim Weischenfeldt, Tobias Ehrenberger, Susanne Gröbner, Maia Segura-Wang, Thomas Zichner, Vasilisa A. Rudneva, Hans-Jörg Warnatz, Nikos Sidiropoulos, Aaron H. Phillips, Steven Schumacher, Kortine Kleinheinz, Sebastian M. Waszak, Serap Erkek, David T. W. Jones, Barbara C. Worst, Marcel Kool, Marc Zapatka, Natalie Jäger, Lukas Chavez, Barbara Hutter, Matthias Bieg, Nagarajan Paramasivam, Michael Heinold, Zuguang Gu, Naveed Ishaque, Christina Jäger-Schmidt, Charles D. Imbusch, Alke Jugold, Daniel Hübschmann, Thomas Risch, Vyacheslav Amstislavskiy, Francisco German Rodriguez Gonzalez, Ursula D. Weber, Stephan Wolf, Giles W. Robinson, Xin Zhou, Gang Wu, David Finkelstein, Yanling Liu, Florence M. G. Cavalli, Betty Luu, Vijay Ramaswamy, Xiaochong Wu, Jan Koster, Marina Ryzhova, Yoon-Jae Cho, Scott L. Pomeroy, Christel Herold-Mende, Martin Schuhmann, Martin Ebinger, Linda M. Liau, Jaume Mora, Roger E. McLendon, Nada Jabado, Toshihiro Kumabe, Eric Chuah, Yussanne Ma, Richard A. Moore, Andrew J. Mungall, Karen L. Mungall, Nina Thiessen, Kane Tse, Tina Wong, Steven J. M. Jones, Olaf Witt, Till Milde, Andreas Von Deimling, David Capper, Andrey Korshunov, Marie-Laure Yaspo, Richard Kriwacki, Amar Gajjar, Jinghui Zhang, Rameen Beroukhim, Ernest Fraenke, Jan O. Korbel, Benedikt Brors, Matthias Schlesner, Roland Eils, Marco A. Marra, Stefan M. Pfister, Michael D. Taylor & Peter Lichter.

    Funding: The MAGIC project is partially financially supported by the Terry Fox Research Institute. M.D.T. is supported by the Garron Family Chair in Childhood Cancer Research, and grants from the Cure Search Foundation, the National Institutes of Health (R01CA148699 and R01CA159859), the Pediatric Brain Tumor Foundation, the Terry Fox Research Institute, and b.r.a.i.n.child. This work was also supported by a Program Project Grant from the Terry Fox Research Institute. 

    TFRI LINKS, Summer 2017
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