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  • TFRI Now Seeking Applications for its 2019 Cancer Research Programs

    by Peter Mothe | May 14, 2018
    rfa


    The Terry Fox Research Institute (TFRI) is seeking applications for two of its prestigious grant programs: The Terry Fox New Frontiers Program and the Terry Fox New Investigators Awards. 

    Both peer-reviewed grant programs focus on supporting excellence and collaboration in cancer research. They're main goal is to move discoveries from the laboratory to the clinic more quickly for the benefit of cancer patients.

    Terry Fox New Frontiers Program

    The Terry Fox New Frontiers Program Project Grants is a long‐standing program involving the best cancer researchers in Canada. These programs support Canadian research teams exploring new frontiers in cancer research (i.e., breakthrough and transformative biomedical, clinical and translational research which may form the basis for innovative cancer prevention, diagnosis and/or treatment).

    New Applicants
     for the Terry Fox New Frontiers Program Project Grants may be supported for a maximum of four years, with a budget of up to $400,000 in the first year followed by up to $600,000 per year for the next three years. Meanwhile, renewing applicants may receive up to $1,000,000 per annum for a maximum of six years

    Current recipients include:

    Program Dates funded Program lead(s)
    Exploiting Pathogenic Mechanisms in Acute Leukemia for Clinical Translation 2017-2022 Karsan, Aly
    Canadian Oncolytic Virus Consortium (COVCo) 2017-2022 Bell, John
    Nanoparticle-Enhanced Photoacoustic Imaging for Cancer Localization and Therapeutic Guidance 2017-2022 Zheng, Gang
    Delineating Therapeutic Opportunities in Triple-Negative Breast Cancer 2016-2019 Lupien, Mathieu
    Targeting clonal heterogeneity in treatment-refractory glioblastoma with novel and empiric immunotherapies 2016-2019 Singh, Sheila
    Targeting the Hippo Signaling Network in Cancer
    2016-2019 Wrana, Jeff
    Targeting the adaptive molecular landscape in castrate-resistant prostate cancer
    2016-2021 Gleave, Martin
    Overcoming Treatment Failure in Lymphoid Cancers 2016-2021 Connors, Joseph
    Development of Stemness-Based Prognostic Biomarkers and Therapeutic Targets 2015-2020 Dick, John
    Oncometabolism and the Molecular Pathways that Fuel Cancer 2015-2019 Giguere, Vincent
    Killing the Hydra: genetic dissection of actionable targets required for maintenance of metastatic disease 2011-2019 Egan, Sean
    A research pipeline for hypoxia-directed precision cancer medicine 1999-2019 Bristow, Robert; Wouters, Bradly
    Li-Fraumeni Syndrome: Applying Genetic Determinants of Cancer Risk to Cancer Surveillance and Prevention 2015-2018 Malkin, David
    Discovery and Therapeutic Development of Antibody-Based Targets in Oncology 2015-2018 Jones, Steven
    Genomics of forme fruste tumours: new vistas on cancer biology and management 2010-2018 Huntsman, David


    For more information
    on the Terry Fox New Frontiers Program 2019 grants, including application guidelines and deadlines, please visit the award site:

    Terry Fox New Investigator Awards

    The Terry Fox New Investigators Awards provides research operating grant support to future leaders as they develop their independent careers in cancer research. Designed to provide a single research grant to scientific and clinical investigators within the first five years of a first faculty-level appointment in Canada, new investigators have to be sponsored and mentored by an existing Terry Fox funded program.

    The 2019 Terry Fox New Investigators Awards add up to $150,000 per annum, and are tenable for three years.

    Current recipients include:

    Name Start/End Project
    Trevor Pugh
    2017-2020 Single cell dissection and non-invasive monitoring of childhood cancer
    Housheng Hansen He
    2017-2020 Understanding the function of circular RNA in tumour hypoxia
    Frederick Antoine Mallette
    2017-2020
    Deciphering the oncogenic properties of cancer-associated IDH1/2 mutations
    Peter Stirling
    2017-2020
    Functionalizing SWI/SWF chromatin remodeller mutations in rare and common tumours
    Guy Ungerechts
    2016-2019 Next Generation Cancer Immunovirotherapy: Heterologous oncolytic prime-boost enhanced with select immunomodulators
    Ralph DaCosta
    2016-2019 Investigating radiation responses of pancreatic tumours, their vasculature and microenvironment using in vivo imaging to identify new treatment strategies
    William Lockwood
    2016-2019 Assessing the effect of radiation from screening low dose CT scans on lung cancer development and progression
    Byram Bridle
    2015-2019
    NCE
    Evaluation of oncolytic immunotherapy in canine cancer trials: A stepping stone towards successful translation into human patients
    Martin Hirst

    2015-2018
    NCE

    Epigenetic basis of acute myeloid leukemia

    Ryan Morin

    2015-2018
    NCE

    Exploring Clonal Evolution in Non-Hodgkin Lymphomas Using Serial Tumour Sampling and Liquid Biopsies

    Sachin Katyal
    2018-2021 Targeting resistant glioblastoma multiforme rGBM) through suppression of overactive DNA repair activity
    Robert Kridel
    2018-2021 Dissecting biological hererogeneity in follicular lymphoma into clinically relevant molecular subtypes
     

    For more information on the 2019 New Investigator Awards, including application guidelines and deadlines, please visit the award site:

  • TFRI-funded researchers uncover “evolutionary arms race” between cancer and immune system

    by Peter Mothe | May 10, 2018

    Shah_SohrabNelson_Brad

    Doctors Sohrab Shah and Brad Nelson are two of the TFRI-funded researchers who participated in the study.  

    A new study led by a team of TFRI-funded researchers has uncovered the mechanisms used by deadly ovarian cancer cells to escape the immune system, setting the stage for a better understanding of how and why patients respond to promising new immunotherapies. 

    Immunotherapy stimulates the patient's own immune system to recognize and destroy tumour cells. It is yielding remarkable outcomes for cancer patients to date and is by far one of the most exciting and active areas of modern cancer care and research.

    The study published today in the scientific journal Cell used advanced molecular and computational techniques to analyze how tumour cells in patients with high-grade serous ovarian cancer (HGSC) the most common and lethal subtype of epithelial ovarian cancers —escape attack from immune cells.

    “Our findings reveal fundamentally new insights into the cause and consequences of ovarian cancer and immune cell interaction,” said Dr. Sohrab Shah, a senior scientist at BC Cancer, a UBC associate professor and senior author of the study. “The results provide a new lens through which we can interpret a host of recently launched ovarian cancer immunotherapy clinical trials around the world.”

    The team of interdisciplinary researchers used advanced molecular measurements and computer algorithms to analyze how immune cells (aka, white blood cells) infiltrate tumours. They “zoomed in” to get a better look at the spaces between the immune and cancer cells to see the proteins present on their surfaces. And they sequenced DNA to understand genetic changes that took place within cancer cells after interacting with immune cells.

    “Our findings reveal an evolutionary arms race between immune cells and HGSC cells,” said Allen Zhang, a UBC MD/PhD student at BC Cancer and the lead author on the study. “As the immune system mounts an attack on a tumour, some cancer cells are eliminated while others evolve and change to resist attack from immune cells. This may help us understand why HGSC often responds poorly to current immunotherapies.”

    Killer T cells are a subtype of immune cell that have the powerful ability to target and destroy infected or cancerous cells. In this study, scientists noticed that a strong Killer T cell infiltration of ovarian tumours was associated with less diversity among the types of cancer cells present in the tumour. This indicated that Killer T cells had successfully tracked and eliminated many of the tumour cells as they evolved but they weren’t able to kill them all, prompting the scientists to take a closer look at the cells that managed to escape.

    They identified combinations of genetic changes that help HGSC cells escape attack from Killer T cells and they plan to use this knowledge in the development of more powerful experimental immunotherapies, including T cell therapy, for gynecological cancers. T cell therapy involves extracting the patient’s own T cells, conditioning or engineering them to recognize and kill cancer cells and infusing large numbers of those programmed cells back into the patient’s body.

    We’ve known for several years that many ovarian cancer patients launch a strong immune response against their tumours, yet this response often fails to control tumour growth over the long-term,” said Dr. Brad Nelson, a distinguished scientist at BC Cancer and co-senior author of the study. “This study has revealed the different tricks used by HGSC tumours to escape from the immune system, leading to exciting new ideas for engineering more potent immune responses that can overcome these various escape mechanisms.”

    Inspired by success in treating other cancers especially in most types of advanced leukemia, BC Cancer’s Immunotherapy Team, led by Drs. Brad Nelson and Rob Holt, is ready
    to launch the first of a series of clinical trials for ovarian and other gynecological cancers.  

    TFRI is one of several funders of the work. 

    The study
    , Interfaces of malignant and immunologic clonal dynamics in ovarian cancer, is available from Cell, here: https://bit.ly/2jLs8qV

    Quick Facts:
     

    • More than 300 women are diagnosed with ovarian cancer each year in British Columbia. 
    • Approximately 250 women in the province die from ovarian cancer each year. 
    • HGSC is the most malignant form of ovarian cancer and accounts for up to 70 per cent of all ovarian cancer cases. 
    • 80 per cent of women diagnosed with HGSC relapse despite an initial response to treatment. 
  • Canadian leaders in tumour hypoxia shed light on the role of mTOR signalling in prostate cancer development

    by TFRI Admin | May 01, 2018
    Istock prostatecancer

    More findings from TFRI’s prestigious hypoxia team are continuing to change the cancer research landscape when it comes to understanding the role of the mTOR signalling pathway in the development and aggressiveness of prostate cancer.

    The group’s latest study, led by Dr. Brad Wouters (Princess Margaret Cancer Centre, University Health Network, Toronto) and published in Molecular Cancer Research (February 2018), highlights two key findings. The first is that the mTOR targets 4E-BP1 and 4E-BP2 proteins play a tumour suppressive function even in the context of constitutive PI3K activation driven by PTEN loss in prostate cancer. Their deletion accelerates tumorigenesis, or the production of tumours. The mTOR signalling pathway is a central regulator of protein synthesis and cellular metabolism that responds to the amount of energy, nutrients, oxygen, and growth factors available. The new study demonstrates it retains aspects of this role even in the case of its deregulation.

    The second key finding is that these same two proteins, and the mTOR pathway, play a key role in the survival of hypoxic cells in these tumours. Patients respond poorly to treatment if their tumours are low in oxygen (hypoxic), and these tumours are more likely to grow and spread aggressively. The ability to restrain mTOR signalling during hypoxia, even in the context of upstream PI3K activation driven by PTEN loss, is essential for the survival of hypoxic cells. Thus, despite the more rapid tumour development in mice lacking these genes, the tumours that develop have lower levels of hypoxia.

    The findings of the present study shed light on key upstream pathways that regulate hypoxia tolerance and thus the establishment of aggressive tumours in prostate cancer. Targeting the pathways that regulate mTOR activation, which is a common strategy in many cancers, may thus influence the formation of therapy resistant and aggressive hypoxic cells.

    Prostate cancer is the most common type of cancer affecting Canadian men, and is the third leading cause of death amongst this demographic.

    Study: The mTOR Targets 4E-BP1/2 Restrain Tumor Growth and Promote Hypoxia Tolerance in PTEN-driven Prostate Cancer

    Authors:
    Mei Ding, Theodorus H. Van der Kwast, Ravi N. Vellanki, Warren D. Foltz, Trevor D. McKee, Nahum Sonenberg, Pier P. Pandolfi, Marianne Koritzinsky, and Bradly G.Wouters.

    Funding: This study was partially funded by a long-term grant from The Terry Fox Research Institute.

    Links #6

     

     

     

     

     


  • Schedule announced for Atlantic Node's Workshop on "The Many Ways to Science"

    by TFRI Admin | Apr 25, 2018

    WorkshopBanner

    TFRI's Atlantic Node and the Beatrice Hunter Cancer Research Institute (BHCRI) will be holding a joint workshop on Friday, May 25 for researchers and students in Atlantic Canada. The subject of the workshop will be "The Many Ways to Science," and will include sessions such as "Tips on the Transition into Industry" and "Alternative Careers in Science," among others.  

    According to the event page, the workshop "was developed to enhance the training of cancer research trainees, but with presentations of interest to anyone in the field of cancer research."

    This year's event will be held at the Collaborative Health Education Building (CHEB) (Room C170) in Halifax, NS. Registration starts at 8:30.

    The event's schedule can be found here. For more information, click here
     





  • TFRI New Investigator searches for follicular lymphoma subtypes to guide patient management

    by TFRI Admin | Apr 06, 2018
    Kridel,R_UHN3181


    One of the most frustrating parts of Dr. Robert Kridel’s work is not being able to tell patients diagnosed with follicular lymphoma if they will respond well to treatment or not – a reality he hopes to change through research during his three-year, $450,000 TFRI New Investigator Award.

    “We know that not every patient does the same during treatment: some do well with minimal therapy, some require much more intensive therapy, and some don’t respond and ultimately die from this disease,” says Dr. Kridel, a clinician-scientist based at Princess Margaret Cancer Centre. “If we could determine up front which patients were higher risk we might be able to adapt our treatment, and hopefully improve outcomes for patients.”

    Around 2,500 Canadians will be diagnosed with follicular lymphoma this year, and all these individuals will receive the same cancer treatment. Patient outcomes for this largely incurable disease remain variable: some remain cancer-free for a decade or more, while others experience rapid disease progression and poor outcome.

    Dr. Kridel is working with a team of lymphoma researchers across Canada to accrue and genetically analyze 200 patient tumour samples to identify different subtypes of the disease. The group has already discovered that patients expressing a gene called FOXP1 have a strikingly different outcome post-treatment than patients without the gene.

    “Having this preliminary data in hand makes me quite confident we’ll be successful in identifying differences between patients that are really meaningful, and guide patient management,” Dr. Kridel notes. “The most exciting aspect is that in a few years we might be able to change the way we treat patients by identifying molecular subtypes of follicular lymphoma that are different based on biology and outcome.”

    Dr. Joseph Connors, clinical director of Vancouver’s Centre for Lymphoid Cancer at BC Cancer, is Dr. Kridel’s mentor for the duration of the award.

    “[Dr. Kridel] is a diligent, thorough and meticulous researcher and has built well on his prior clinical and academic experience to prepare for a very productive career in academic medicine,” says Dr. Connors. “I am confident he will become a solid contributor within the community of lymphoid cancer researchers and am delighted his career is off to such a promising start.”

    The opportunity to collaborate with leading lymphoid cancer researchers such as Dr. Connors is one of the most valuable aspects of the New Investigator Award, Dr. Kridel adds.

    “We are always much stronger working together than against each other in science,” he says. “This is the kind of project no single group can do, and it’s typically the effort of teams working together across Canada. We hope our findings will have a meaningful impact on patient lives.” 

    Project Title: Dissecting Biological Heterogeneity in Follicular Lymphoma into Clinically Relevant Molecular Subtypes

    Award: $450,000 over three years

    Mentoring Program: The Terry Fox New Frontiers Program Project Grant in Overcoming Treatment Failure in Lymphoid Cancers (2016-2021)

     
  • Terry Fox Research Institute awards prestigious grant to help Manitoba cancer researcher tackle deadly brain cancer

    by TFRI Admin | Mar 07, 2018

    SachinWINNIPEG—Brain cancer research in Manitoba has received a boost with news that a local scientist has won a prestigious cancer research award from the Terry Fox Research Institute.

    Dr. Sachin Katyal, a researcher at CancerCare Manitoba and the University of Manitoba, is the first researcher in Manitoba to receive the $450,000 Terry Fox New Investigator award for his “quick-to-clinic” personalized medicine approach to better treat patients with glioblastoma multiforme (GBM).

    “Everyone’s so excited Manitoba has won a Terry Fox Research Institute award, especially because this province was Terry’s birthplace,” says Dr. Katyal. “Glioblastoma is a pretty insidious disease and is almost like a death sentence -- it’s got fairly grim statistics, and my goal is to change that.”

    He will use his award to analyze resistant brain cancer tumour cells to determine what DNA-damaging enzyme repair proteins are allowing cancer cells to survive following chemotherapy and radiation treatments.

    The project’s findings will have the potential to help people like Manitoban Lawrence Traa, who was diagnosed with glioblastoma more than five years ago. Having a Terry Fox Research Institute project funded in his province is very exciting, he says, both for himself and for future brain cancer patients.  

    “One of the toughest things for glioblastoma patients to come to terms with is that you may die from the disease,” says Traa. “When we hear about research like this being done in Manitoba, it brings us hope.”

    Dr. Victor Ling, TFRI president and scientific director, is pleased to see the three-year award go to a Manitoba researcher. “These awards are given to promising new cancer clinicians and scientists who represent the future of cancer research. The Terry Fox Research Institute funds several major projects aiming to improve outcomes for glioblastoma patients, and we are pleased to support Dr. Katyal’s work in DNA repair to help find cures for this disease.”

    “This research funding and the partnership among the Terry Fox Research Institute, CancerCare Manitoba and the University of Manitoba, ensures the continuation of transformational research that improves patients lives in Manitoba,” adds Dr. Digvir S. Jayas, vice-president (research) and Distinguished Professor at the University of Manitoba.

    “Through this New Investigator award, Dr. Katyal will be able to network with brain cancer researchers across the country with the potential to impact brain cancer patients,” says Dr. Spencer Gibson, Head of Cell Biology at CancerCare Manitoba’s Research Institute and TFRI Prairie Node Lead.

    More than 2,500 Canadians are diagnosed with brain cancer each year, and GBM is the most common -- and aggressive tumour. [Note: In October 2017, Tragically Hip band member Gord Downie died of this disease.]

    NOTE: More information about Dr. Katyal’s research is available online at:http://www.tfri.ca/en/dr-sachin-katyal

    About The Terry Fox Research Institute (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 more than 80 cancer hospitals and research organizations across Canada. TFRI headquarters are in Vancouver, B.C. For more information please visit www.tfri.ca and follow us on Twitter (@tfri_research).

     

  • Canadian pancreatic cancer research team provides personalized medicine, new hope to patients

    by TFRI Admin | Mar 06, 2018
    Image-1

    (From top left to bottom right: Drs. Daniel Renouf, Jennifer Knox, Steven Gallinger, George Zogopoulos, David Schaeffer,, and Oliver Bathe). 

    VANCOUVER – Canadian pancreatic cancer researchers are joining forces under a Terry Fox initiative bringing new hope for patients with this deadly disease.

    “For many years it’s been hopeless from a patient perspective, and we are hoping to help shift this,” says Dr. Daniel Renouf (BC Cancer, University of British Columbia) who, along with Dr. David Schaeffer (UBC, Vancouver General Hospital), is leading a $5-million pan-Canadian, precision medicine initiative recently funded by the Terry Fox Research Institute.

    A lack of early detection tests. Few known symptoms. Very limited treatment options. No known biomarkers that can be used to direct therapy.  These are among the clinical challenges team EPPIC, short for Enhanced Pancreatic Cancer Profiling for Individualized Care, is tackling over the next five years to improve personalized treatments for patients with pancreatic ductal adenocarcinoma (PDAC), a disease with just a nine per cent five-year survival rate.

    “Our project focuses on metastatic cancer versus surgically resectable primary tumours, because this is the clinical problem we see most often,” says Dr. Schaeffer, noting a priority is to discern if the metastatic and primary tumour differ in their genetic make-up. Four out of five patients have metastatic cancer at the time of diagnosis and most will succumb within a year.

    Patients are very keen to participate in the research study. “My push is to keep the support coming for the research, and to bring hope to other pancreatic cancer patients. This is a disease that needs more hope,” says Susan Stewart, 57, a North Vancouver resident who was diagnosed with Stage IV terminal pancreatic cancer in January 2017. She was enrolled immediately in EPPIC as well as a clinical trial where she received an experimental therapy. Although it is early days yet, her results today are promising.  Her pancreatic cancer tumour is no longer visible on CT scans, and the metastatic cancer on her liver has shrunk considerably. Her doctors are using the EPPIC results to try and understand why her tumour has had such an incredible response to the experimental treatment.

    The EPPIC team aims to sequence metastatic pancreatic tumours of 400 patients in Quebec, Ontario, Alberta and British Columbia.  They hope to improve understanding of pancreatic cancer biology to individualize treatment strategies, and to facilitate the development of new treatment options. 

    This project is currently under way in Toronto and Vancouver, through two clinical trials (COMPASS and PanGen), and will be expanded shortly to include eligible patients in Kingston, Ottawa, Calgary, and Edmonton. The Montreal site opens this week. Genomic sequencing and bioinformatics analyses of patient tumours will be conducted at the Ontario Institute for Cancer Research (OICR) and the BC Cancer Genome Sciences Centre.

    The team will also store and analyze the genomic and clinical data collected in a knowledge bank that will be shared by Canadian and international researchers seeking ways to improve treatment.  The bank will be the first of its kind in Canada.

    Dr. Victor Ling, TFRI president and scientific director, is thrilled TFRI is funding this high-calibre precision medicine team to tackle such a hard-to-treat cancer. “Pancreatic cancer research has been historically underfunded, and we are very excited to be expanding such a successful personalized medicine project to patients across Canada.  We hope precision medicine may hold the key to finding better treatments for this incurable disease.”

    EPPIC’s multidisciplinary team comprises clinicians and scientists from BC Cancer, Vancouver Coastal Health Research Institute, University of British Columbia, University of Calgary, University of Alberta, Princess Margaret Cancer Centre, University Health Network, OICR, McGill University Health Centre (MUHC) and the Research Institute of MUHC, Centre hospitalier de l’Université de Montréal, Queen’s University and the Ottawa Hospital.

    In addition to Drs. Renouf and Schaeffer, other principal investigators of EPPIC and the COMPASS and PanGen trials are: Dr. Jennifer Knox and Steven Gallinger (Princess Margaret Cancer Centre/UHN/ OICR), Dr. George Zogopoulos (MUHC/Research Institute of MUHC/McGill University), and Dr. Oliver Bathe (Tom Baker Cancer Center, University of Calgary). Many of the team’s investigators are members of PancOne™, an initiative of Pancreatic Cancer Canada (PCC).

    TFRI’s investment in EPPIC also builds on funding from BC Cancer Foundation, OICR, Princess Margaret Cancer Foundation, PCC and VGH and UBC Hospital Foundation.

    Read the story from McGill University Health Centre here

    Patient Eligibility

    EPPIC is for patients with advanced pancreas adenocarcinoma who have not yet started their first-line chemotherapy. Their oncologist can potentially access the trials by contacting the groups directly. The trial information can be found online by their oncologist at: 

    COMPASS trial: https://www.clinicaltrials.gov/ct2/show/NCT02750657?term=02750657&rank=1  

    PANGEN trial:  https://www.clinicaltrials.gov/ct2/show/NCT02869802?term=02869802&rank=1


    About The Terry Fox Research Institute (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 more than 80 cancer hospitals and research organizations across Canada. TFRI headquarters are in Vancouver, B.C. For more information please visit www.tfri.ca and follow us on Twitter (@tfri_research).

    Media Contacts

    Kelly Curwin, 604-675-8223; 778-237-8158 (cell) kcurwin@tfri.ca

    EPPIC BACKGROUNDER

    • Pancreatic cancer is the fourth most common cause of cancer-related death in Canada, and affects 5,500 patients a year. In Canada, cancer pancreatic rates are projected to double by 2030.

    • Eighty per cent of patients have metastatic cancer at the time of diagnosis, yet the majority of pancreatic cancer research is only done on the primary tumour.

    • In the United States, pancreatic cancer has just surpassed breast cancer in terms of fatality to become the third most common cause of cancer-related deaths.

    • EPPIC will use an “omics” approach to help advance progress in precision medicine for these patients which will include a detailed molecular analysis of their tumours. In addition, the team will examine each patient’s tumour(s) genome, transcriptome, proteome and metabolome.

    • The team hopes to identify subtypes of the disease based on the above analyses as well as predictive signatures and biomarkers to help individualize treatment, diagnose the disease earlier, and better manage treatment and treatment response.

    • Over the course of the study, the team hopes outcomes will be improved by guiding patients into specific clinical trials in real time.

    • Patients are already enrolled in two sites currently operating and these trials will be expanded to the other identified study sites:

      • The COMPASS trial operates at the Princess Margaret in Toronto and is funded by the Ontario Institute for Cancer Research and Pancreatic Cancer Canada (PCC) NB: Early results from this trial have been positive in demonstrating that sequencing can be performed in a clinical setting and results delivered within a clinically relevant time frame to help guide individual patient treatment.

      • The PanGen trial operates at BC Cancer in Vancouver as part of the Personalized Oncogenomics Program and has been/ is funded by BC Cancer Foundation and PCC.

  • Therapeutic target EZH2 discovered for aggressive, untreatable ovarian cancer affecting young women

    by TFRI Admin | Feb 15, 2018

    Dr. Hunstman

    A Vancouver team led by TFRI-funded investigator Dr. David Huntsman has discovered an important therapeutic target for treating small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). This is a rare, but extremely lethal, ovarian cancer in young women with no effective treatment.

    The present study, published in The Journal of Pathology (June 2017), suggests that SCCOHT tumour cells need the activity of an enzyme called EZH2 for their survival. This enzyme adds methyl groups to the dedicated site of histones, a group of proteins that maintain the proper structure of DNA, and thereby controls which genes to turn on or off.

    Two EZH2 inhibitors (GSK126 and EPZ-6438), in various trials, displayed robust pre-clinical activities against SCCOHT tumour, and are therapeutic targets with the potential to help patients living with this disease. The median age of diagnosis is 24; most women succumb within two years.

    Further, the synthetic lethality between the deficiencies in a multi-protein complex called SWI/SNF chromatin remodeling complex and EZH2 inhibition has been proposed. The present study provided solid evidence supporting this notion in the context of a rare ovarian cancer that is fully driven by complete loss of the enzymatic activity of SWI/SNF complex. The findings also suggest that the deficiency of SWI/SNF complex alone is not sufficient to predict cellular sensitivity to EZH2 inhibition and the cellular context does play an important role.

    Looking forward, the team is working to identify "molecular markers" to predict the response of SCCOHT tumours to EZH2 inhibitors. By seeing which markers are present in patients, researchers can determine the SCCOHT patients that will benefit from the treatment. One of the biggest risks of treating cancer patients with a single drug is the almost inevitable development of resistance to that drug. With this in mind, the group will develop strategies that can improve the efficacy of EZH2 inhibitor treatment alone.

    Study: The histone methyltransferase EZH2 is a therapeutic target in small cell carcinoma of the ovary, hypercalcaemic type.

    Authors: Yemin Wang, Shary Yuting Chen, Anthony N Karnezis, Shane Colborne, Nancy Dos Santos, Jessica D Lang, William PD Hendricks, Krystal A Orlando, Damian Yap, Friedrich Kommoss, Marcel B Bally, Gregg B Morin, Jeffrey M Trent, Bernard E Weissman and David G Huntsman.

    Funding: This study was funded in part by the Terry Fox Research Institute’s New Frontiers Program Project Grant in the genomics of forme fruste tumours; new vistas on cancer biology and treatment.

  • Made-in-Canada model for detecting lung cancer saves lives, is a world leader

    by TFRI Admin | Feb 15, 2018

    Dr. Lam Picture

    A pan-Canadian TFRI 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 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 Lancet Oncology (Oct. 17, 2017), were also presented at the 18th World Conference on Lung Cancer in Japan by co-principal investigator Dr. Stephen Lam (chair of British Columbia’s Provincial Lung Tumour Group at BC Cancer and a professor of medicine at the University of British Columbia).

    The Pan-Can Lung Cancer Risk-Prediction Model – which is used to determine which individuals 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 U.S.). The Pan Can 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.

    Currently, both the U.S. 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. 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.

    Lung cancer is the most common cause of cancer death around the world with one of the worst survival rates, yet if caught early enough it can be cured in 70 per cent of cases. An accurate predictive model to select candidates who would benefit from CT screening is crucial. The Pan Can Model was developed with $8.4-million support from TFRI and The Canadian Partnership Against Cancer. 

    Study: Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

    Authors: Martin C Tammemagi, Heidi Schmidt, Simon Martel, Annette McWilliams, John R Goffin, Michael R Johnston, Garth Nicholas, Alain Tremblay, Rick Bhatia, Geoffrey Liu, Kam Soghrati, Kazuhiro Yasufuku, David M Hwang, Francis Laberge, Michel Gingras, Sergio Pasian, Christian Couture, John R Mayo, Paola V Nasute Fauerbach, Sukhinder Atkar-Khattra, Stuart J Peacock, Sonya Cressman, Diana Ionescu, John C English, Richard J Finley, John Yee, Serge Puksa, Lori Stewart, Scott Tsai, Ehsan Haider, Colm Boylan, Jean-Claude Cutz, Daria Manos, Zhaolin Xu, Glenwood D Goss, Jean M Seely, Kayvan Amjadi, Harmanjatinder S Sekhon, Paul Burrowes, Paul MacEachern, Stefan Urbanski, Don D Sin, Wan C Tan, Natasha B Leighl, Frances A Shepherd, William K Evans, Ming-Sound Tsao, Stephen Lam, for the Pan Can Study Team*

    Funding: Terry Fox Research Institute and Canadian Partnership Against Cancer

  • Nuclear mTOR acts as a transcriptional regulator of metabolism in prostate cancer, groundbreaking study finds

    by TFRI Admin | Feb 15, 2018

    Giguere_TFRI_Figure

    A recent study by TFRI’s cancer metabolism group suggests nuclear mTOR (a kinase) also works as a transcriptional regulator of metabolism in the proliferation of prostate cancer. Their findings underscore a shift in our understanding of the androgen receptor (AR) as the master transcriptional regulator of metabolism in prostate cancer. 

    Dr. Vincent Giguère (McGill University) is the corresponding author of an important Genes and Development paper (August 2017), which sheds light on how prostate cancer develops, survives, and grows. Results showed that mTOR, a regulator of cellular metabolism well-known for its activity in the cytoplasm, also works in the nucleus to directly affect the expression of metabolic genes.

    Their paper suggests mTOR co-operates directly with the androgen receptor to regulate the expression of these genes. Together, the combined action of nuclear mTOR and the AR reprograms the metabolism of prostate cancer cells to favour their growth and proliferation. The team’s findings have brought a new understanding to the molecular mechanisms and the factors involved in promoting prostate cancer cell growth via alteration of their metabolism.

    The team also successfully identified an mTOR-dependent gene signature which could help predict recurrence in prostate cancer patients. Prostate cancer is the third leading cause of cancer-related death in Canadian men, and one of the most common cancers for this demographic.

    This knowledge will benefit the development of future combinatorial therapies against both mTOR and AR to treat prostate cancer. Currently, drugs targeting mTOR have not been an effective therapy for prostate cancer. The present paper suggests this could be because they target the cytoplasmic function of mTOR instead of the nuclear function.

    Importantly, the present study covers the whole spectrum of cancer research, from basic mechanisms of gene regulation to the validation of these findings in gene expression data sets obtained from patient materials, as well as the demonstration that the activity of these factors can be targeted by drugs currently in use in the clinic.

    Study: Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer

    Authors: Étienne Audet-Walsh, Catherine R Dufour, Tracey Yee, Fatima Z Zouanat, Ming Yan, Georges Kalloghlian, Mathieu Vernier, Maxime Caron, Guillaume Bourque, Eleonora Scarlata, Lucie Hamel, Fadi Brimo, Armen G Aprikian, Jacques Lapointe, Simone Chevalier, and Vincent Giguère

    Funding: This work was supported in part by a Terry Fox Research Institute New Frontiers Program Project Grant in oncometabolism and the molecular pathways that fuel cancer.

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