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  • Study finds diffuse optical spectroscopic (DOS) texture features can predict breast cancer response prior to neoadjuvant chemotherapy

    by TFRI Admin | Sep 06, 2017

    TFRI IMAGE

    Thanks to advances in imaging, oncologists may one day be able to determine if a patient responds to chemotherapy before receiving treatment. A recent study by a TFRI-funded team has shown that diffuse optical spectroscopic (DOS) texture features can predict breast cancer response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer patients before therapy even begins.

    Led by Dr. Greg Czarnota (Sunnybrook Health Sciences Centre, Ontario), and published in The British Journal of Cancer (April 2017, Dr. William Tran first author), the finding has the potential to guide treatment, improve breast cancer therapeutics, and may even improve overall disease-free survival. Breast cancer is the second leading cause of cancer-related death in women, and nearly 20 per cent of diagnoses are of locally advanced breast cancer – with only half of patients surviving beyond five years.

    Previous research by Dr. Czarnota’s team demonstrated that DOS imaging was capable of monitoring response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. In the present study, researchers set out to evaluate texture features of pre-treatment DOS maps as a way of predicting patient response to NAC.

    Thirty-seven locally advanced breast cancer patients with a median age of 50 were identified, imaged before treatment and categorized as either a responder or a non-responder based on ultimate pathological data.  Breast tissue parametric maps were constructed and texture analyses were performed based on grey-level co-occurrence matrices for feature extraction.

    The results were impressive: for the first time, it was demonstrated that textural heterogeneities in DOS measures of haemoglobin and oxygen content in breast tumours predict NAC response with high accuracy. DOS-based textural parametrics show significant potential as a way of measuring baseline tumour heterogeneity, as well as for markers to measure patient response to chemotherapy treatment. These markers could help personalize medicine for women with breast cancer, and may prevent those who will not respond to therapy from undergoing cytotoxic chemotherapy, guiding these patients instead to alternative treatments.

    Study: Predicting breast cancer response to neoadjuvant chemotherapy using pre-treatment diffuse optical spectroscopic texture analysis

    Authors: William T. Tran, Mehrdad J. Gangeh, Lakshmanan Sannachi, Lee Chin, Elyse Watkins, Silvio G Bruni, Rashin Fallah Rastegar, Belinda Curpen, Maureen Trudeau, Sonal Gandhi, Martin Yaffe, Elzbieta Slodkowska, Charmaine Childs, Ali Sadeghi-Naini and Gregory J. Czarnota.

    Funding:  This project was funded by the Terry Fox Research Institute, Canada.

    TFRI LINKS, Summer 2017
  • Why does relapse occur in aggressive leukemia? Canadian researchers crack the case

    by TFRI Admin | Sep 06, 2017

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    For decades scientists and physicians have wondered what causes some people with cancer to relapse after an apparently successful course of treatment. Now a team of Canadian cancer researchers has discovered the answer to this age-old question, showing that rare and therapy-resistant leukemia stem cells are already present at diagnosis – well before any treatment has begun - in patients who experience relapses of acute myeloid leukemia (AML).

    The team, led by TFRI-funded Dr. John Dick (a senior scientist at Princess Margaret Cancer Centre), recently had their findings published in Nature (June 2017). There are two distinct cancer stem cell populations that can lead to relapse in AML, the paper suggests, rare therapy-resistant cells present at diagnosis that have the ability to regrow the disease in patients. AML is the deadliest form of leukemia, with cure rates significantly lower than some other forms of the disease.

    The team used an innovative, two-part approach for the study. Paired patient samples of blood taken at the initial clinic visit before treatment as well as after treatment when the disease recurred were analyzed to see what similarities and differences existed between samples. Detailed genetic studies were undertaken, and whole genome sequencing was used to examine every part of the DNA at diagnosis and at relapse to see in which cells genetic changes were occurring.

    Most people diagnosed with AML have 10 mutations in their leukemia cells, while some normal stem cells have up to three different mutations. Researchers in the present study were able to determine which mutations were only seen at relapse, using the team’s pre-existing knowledge of leukemic and normal stem cells to discover two cells types that can cause relapse.

    This finding builds onto a paper the team published in Nature in December 2016, which discovered a 17-gene signature derived from leukemia stem cells to predict at diagnosis which AML patients will respond to standard treatment and which will not. These new biomarkers have the potential to lead to clinical trials for targeted types of chemotherapy, compared to the one size fits all treatment AML patients currently receive.  

    Study: Tracing the origins of relapse in acute myeloid leukemia to stem cells

    Authors: Liran I. Shlush, Amanda Mitchell1, Lawrence Heisler, Sagi Abelson, Stanley W. K. Ng, Aaron Trotman-Grant, Jessie J. F. Medeiros, Abilasha Rao-Bhatia, Ivana Jaciw-Zurakowsky, Rene Marke, Jessica L. McLeod, Monica Doedens, Gary Bader, Veronique Voisin, ChangJiang Xu, John D. McPherson, Thomas J. Hudson, Jean C. Y. Wang, Mark D. Minden & John E. Dick.

    Funding: This work was supported by grants from the Ontario Institute for Cancer Research with funds from the Province of Ontario, the Cancer Stem Cell Consortium with funding from the Government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-047), and the Canadian Institutes of Health Research (CSC-105367), the Canadian Cancer Society, The Terry Fox Foundation, a Canada Research Chair to J.E.D. L.I.S. was funded by the Benjamin Pearl Fellowship from the McEwen Centre for Regenerative Medicine and an American Society of Hematology Scholar Award. This research was funded in part by the Ontario Ministry of Health and Long-Term Care, whose views are not expressed here.

    TFRI LINKS, Summer 2017 

  • TP53 polymorphisms and MDM2 SNP309 are not correlated with pre-menopausal cancer risk, study suggests

    by TFRI Admin | Sep 06, 2017

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     While significant accolades are given to scientists who discover genetic mutations that are linked to cancer, it is equally important to determine factors that are not correlated – something that is the focus of a new Canadian study team investigating polymorphisms and risk of pre-menopausal breast cancer.

    Only around five per cent of women diagnosed with breast cancer are under the age of 40, and of this population around five to eight per cent carry a germline (hereditary) mutation to the tumour suppressor gene. However, little research has been done on why early-onset breast cancer occurs in women without any apparent hereditary link. Hence, the study authors  (Human Mutation, January 2017) set out to examine the composite effects of TP53 variants (TP53 PIN3 and SNP309 of MDM2) on early-onset cancer risk in women without mutations to TP53 or the hereditary breast cancer-associated genes, BRCA1 and BRCA2.

    Led by Dr. David Malkin (The Hospital for Sick Children, Toronto), they assessed the spectrum of polymorphisms in TP53 and its negative regulatory gene, MDM2 in 40 female patients with pre-menopausal breast cancer. No significant correlation was found, and while one polymorphism was frequently found in the cohort, it was not associated with the risk of developing cancer before the age of 35 years in an extended cohort of 1,420 breast cancer cases. The study (first author Dr. Nardin Samuel) also showed that functional studies of the rs1800372:A>G polymorphic allele reveal it does not affect p53 transactivation function.

    While these findings suggest early-onset breast cancer is believed to be related to strong genetic predisposition, this cannot be attributed to TP53 polymorphisms alone, or MDM2 SNP309:T>G in the population surveyed. Many patients in the study’s cohort had an extensive familial – and often personal –  history of cancer despite testing negative for pathogenic mutations in TP53, and it is possible underlying genetic susceptibilities may exist. For example, polymorphic variants that contribute to risk may exist in the well-known cancer susceptibility genes CDH1, PTEN, STK11, and NF1.

    Looking forward, researchers suggest genome-wide sequencing of germline mutations and variants in larger patient cohorts may be a good approach to identifying novel driver genes. Further, continuing the search for answers in the underlying heritability of early-onset breast cancer risk will be crucial to better understand why some women get cancer at such a young age.

    Study: Assessment of TP53 polymorphisms and MDM2 SNP309 in pre-menopausal breast cancer risk

    Authors: Nardin Samuel, Badr Id Said, Tanya Guha, Ana Novokmet, Weili Li, Laxmi Silwal-Pandit, Anne-Lise Børrsen-Dale, Anita Langerød, Thomas J. Hudson, and David Malkin.

    Funding: Contract grant sponsors: Canadian Institutes for Health Research (CIHR); The Terry Fox Research Institute/Foundation; SickKids Foundation; Ontario Institute for Cancer Research, Ontario Ministry of Research and Innovation (Senior Investigator Award); Vanier Canada Graduate Scholarship through CIHR.

    TFRI LINKS, Summer 2017
  • Subtype-specific alterations in BCL2 linked to poor post-treatment outcomes in non-Hodgkin lymphoma

    by TFRI Admin | Sep 06, 2017

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    TFRI funding for researchers at the Centre for Lymphoid Cancer (BC Cancer Agency) has resulted in the discovery that subtype-specific alterations in a driver gene for non-Hodgkin lymphoma (BCL2) is strongly associated with poor patient outcomes after treatment.

    The work by Drs. David Scott, Randy Gascoyne, Joseph Connors, and Christian Steidl was published in Blood (May 2017). Diffuse large B-cell lymphoma (DLBLC) is the most common type of non-Hodgkin lymphoma, predominantly affecting people in their mid-60s. BCL2 and MYC are critical driver genes for the disease and play key roles in in normal B-cell differentiation and tumourigenesis.

    Genetic alterations in both genes were profiled in the present study via next-generation sequencing and high-resolution SNP array in 347 de novo DLBCL patients that had already been treated with R-CHOP, the standard chemotherapy treatment for this disease. The team discovered the clinical impact of genetic aberrations in DLBLC needs to be placed in the context of the cell-of-origin molecular subtype and, when this is done, subtype-specific alterations in BCL2 are revealed as being strongly associated with poor outcomes post treatment.

    Further, this work showed that the incidence of MYC/BCL2 genetic alterations and their clinical significance were mainly dependent on cell-of-origin (COO) subtypes. There are two main subtypes of DLBLC based on COO, activated B-cell-like (ABC) subtype and the germinal center B-cell-like (GCB) subtype, both of which have different biology and clinical behaviour. In ABC and GCB subtypes, gain of BCL2 and translocation of BCL2 respectively often led to poor outcomes. The results suggest that COO subtype-specific biomarkers based on these BCL2 genetic alterations can be effectively used to risk-stratify patients with DLBCL treated with immunochemotherapy.

    This paper highlights the value of examining clinical correlates in large homogeneously treated population registry-based cohorts. The finding that BCL2 dysregulation is a common feature of patients with inferior survival will prioritize examination of therapeutic approaches that target BCL2, and hopefully result in better patient outcomes in the future.

    Study: Genetic profiling of MYC and BCL2 in diffuse large B-cell lymphoma determines cell-of-origin–specific clinical impact

    Authors: Daisuke Ennishi, Anja Mottok, Susana Ben-Neriah, Hennady P. Shulha, Pedro Farinha, Fong Chun Chan, Barbara Meissner, Merrill Boyle, Christoffer Hother, Robert Kridel, Daniel Lai, Saeed Saberi, Ali Bashashati, Sohrab P. Shah, Ryan D. Morin, Marco A. Marra, Kerry J. Savage, Laurie H. Sehn, Christian Steidl, Joseph M. Connors, Randy D. Gascoyne, and David W. Scott.

    Funding: This study was supported by a Program Project Grant from the Terry Fox Research Institute (Grant No. 1023 to R.D.G.)

    TFRI LINKS, Summer 2017
  • Discovery of seven new ovarian cancer subtypes opens door for more targeted treatments

    by TFRI Admin | Sep 06, 2017

    Dr. Shah

    The discovery of seven new genetic subtypes of ovarian cancer may lead to targeted treatments for women diagnosed with this disease, including those with the most malignant form and those who do not respond well to current chemotherapy treatments.

    The findings by a group of TFRI-funded scientists led by Dr. Sohrab Shah, senior scientist at the BC Cancer Agency, were published in Nature Genetics (May 2017, Dr. Yi Kan Wang first author). The new subtypes included two from high grade serous cancer (HGSC), the most malignant form, thought to originate in the fallopian tube with early evolutionary acquisition of TP53 mutation and LOH of chromosome 17. These account for up to 70 per cent of all ovarian cancer cases, and 80 per cent of women relapse despite initial treatment success. The other five new subtypes were discovered from three other tumour types: clear cell (CCOC), endometrioid (ENOC), and adult granulosa cell (GCT).

    For the study, tumours from 133 patients with ovarian cancer were subjected to whole-genome sequencing to identify abnormalities in the DNA of ovarian cancer cells. The whole-genome point mutation and structural variation patterns were examined. The study suggests a sub-group of HGSC tumours may have increased capacity to repair events induced by genotoxic chemotherapy. This could explain why these cancers may not be responsive to PARP inhibitors and, in the independent cohorts presented here, show evidence of poor response to the chemotherapy drug cisplatin (typically used to treat ovarian cancer).

    The results show a new stratification of the major histotypes of ovarian cancer using the tumour genome as a biomarker. The genome as a whole reflects aberrant DNA repair processes and thus can be used as means of identifying new therapeutic targets that transcends traditional gene-based biomarkers such as BRCA1 or BRCA2.    

    Further, patterns of changes across the DNA inside cancer cells can help direct drug development efforts for the hardest-to-treat subtypes of ovarian cancer. These findings could be used to develop tests that can direct patients toward new investigational treatments that may help women with subtypes of the disease that are not responsive to standard treatments, as well as illuminate vulnerabilities to exploit in developing future intervention strategies.

    Study: Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes

    Authors: Yi Kan Wang, Ali Bashashati, Michael S. Anglesio, Dawn R. Cochrane, Diljot S. Grewal, Gavin Ha, Andrew McPherson, Hugo M. Horlings, Janine Senz, Leah M. Prentice, Anthony N. Karnezis, Daniel Lai, Mohamed R. Aniba, Allen W. Zhang, Karey Shumansky, Celia Siu, Adrian Wan, Melissa K. McConechy, Hector Li-Chang, Alicia Tone, Diane Provencher, Manon de Ladurantaye, Hubert Fleury, Aikou Okamoto, Satoshi Yanagida, Nozomu Yanaihara, Misato Saito, Andrew J. Mungall, Richard Moore, Marco A. Marra, C. Blake Gilks, Anne-Marie Mes-Masson, Jessica N. McAlpine, Samuel Aparicio, David G. Huntsman & Sohrab P. Shah.

    Funding: We wish to acknowledge generous long-term funding support from the BC Cancer Foundation, supporting the research program of S.P.S. and OvCaRe. The authors graciously thank the Gray Family Ovarian Clear Cell Carcinoma Research Resource, which provided funding critical to this project. Additional funding was provided by a Terry Fox Research Institute New Investigator grant to S.P.S. and a Canadian Cancer Society Research Institute Impact grant to D.G.H. and S.P.S.

    TFRI LINKS, Summer 2017

  • Three 2017 PPG awards announced for cutting-edge projects in leukemia, oncolytic viruses, nanoparticle imaging

    by TFRI Admin | Sep 05, 2017

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    (Top left: Dr. Gang Zheng, bottom right: Dr. John Bell, right: Dr. Aly Karsan).

    The Terry Fox Research Institute has invested nearly $21.5-million to renew three 2017 Terry Fox New Frontiers Program Project Grants (PPGs). The projects, based at three leading cancer institutes across Canada, will investigate acute leukemia, oncolytic viruses, and nanoparticle imaging in cancer interventions respectively over the next five years. 

    The successful teams are:

    • The Terry Fox New Frontiers Program Project Grant in [Canadian Oncolytic Virus Consortium: COVCo]; Principal Investigator: Dr. John Bell, Ottawa Hospital Research Institute;

    • The Terry Fox New Frontiers Program Project Grant in Exploiting Pathogenic Mechanisms in Acute Leukemia for Clinical Translation; Principal Investigator: Dr. 
      Aly Karsan, BC Cancer Agency;

    • The Terry Fox New Frontiers Program Project Grant in Porphysome Nanoparticle-Enabled Image-Guided Cancer Interventions; Principal Investigator: Dr. Gang Zheng, Princess Margaret Cancer Centre.

    PPG awards are designed to bring together leading researchers with complementary skills to investigate different aspects of a given area of cancer research. By bringing individual research projects together under one PPG, results can be realized more rapidly and more efficiently. The 2017 Terry Fox New Frontiers Program Project Grants award winners will be profiled in greater detail shortly.

  • Grab your running shoes: Join us on Sept. 17 for the annual Terry Fox Run

    by TFRI Admin | Aug 28, 2017

    This year's annual Terry Fox Run will be held at locations across Canada on Sunday, Sept. 17. Everyone is welcome to participate, regardless of age, athletic ability or socio-economic standing. While the Run does not have an entry fee or minimum donation we do ask all participants to fundraise or make a donation. You can raise funds online, use a pledge sheet or make a donation at the Run site. Whatever your choice, please know that every dollar counts.

    Visit the Terry Fox Foundation website for more information. 


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  • Canadian hero Terry Fox’s cancer research legacy lives on: VICE Sports

    by TFRI Admin | Jun 30, 2017

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    Two articles published by VICE Sports for Canada 150 are calling Terry Fox the most important athlete in Canadian history whose cancer research legacy lives on.

    “Fox's triumphant Marathon of Hope run was influential in raising much-needed money and awareness for cancer research,” reads the article written by Alex Wong. “His legacy will live on forever, as his impact is still felt across the world today.”

    During the Marathon of Hope, Terry ran 5,000 kilometres across Canada for 143 straight days, all with one leg. Thirty-six years after he passed away from osteosarcoma more than $750-million has been raised in his name for cancer research.

    Founding president and scientific director of The Terry Fox Research Institute Dr. Victor Ling says many doctors and scientists were inspired to enter the profession because of the Marathon of Hope.

    "Because of Terry, and because of who he is, people are willing to work together and collaborate," said Dr. Ling. “We decided we should really do the hard things because that's what Terry would want us to do. He would want us to tackle the biggest challenges."

    To read the full articles and hear more from the Fox family and TFRI-funded researchers, check out:

    Doctors Tell Us How Terry Fox Is Still Influencing Cancer Research

    Terry Fox is the Most Important Athlete in Canadian History

  • Lung cancer screening may save both lives and money, study suggests

    by TFRI Admin | Jun 30, 2017

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    New research from a TFRI-funded team suggests screening for lung cancer could save money – and lives – especially if it also identifies other tobacco-related conditions in high-risk individuals.

    This study was published in the Journal of Thoracic Oncology (May 2017), and suggests combining CT screening for multiple conditions with efforts to stop smoking and manage the treatment of non-cancer heart and lung disease could make screening even more cost-effective.

    Lung cancer is the most common cause of cancer death around the world, with 1.6 million deaths and 1.8 million new cases a year. The five-year for survival rate for patients is currently less than 18 per cent, but if caught early enough the disease can be cured for 70 per cent of cases. 

    Lead author Dr. Sonya Cressman (The Canadian Centre for Applied Research in Cancer Control/BC Cancer Agency) says researchers need to think about how to manage lung cancer while focusing on economically viable strategies such as prevention and screening.

    “Screening those at a high-risk gives us the chance to prevent and treat a range of tobacco-related illnesses, and could also offer access to care for individuals who could be otherwise stigmatized or segregated from receiving treatment,” she said.

    Patient data from two major screening trials was examined: The National Lung Cancer Screening Trial (NLST) and the TFRI Pan-Canadian Early Detection of Lung Cancer Study (PanCan). An economic model was built to simulate the costs and benefits of introducing lung cancer screening programs for high-risk people, or those who had a two per cent or higher chance of developing lung cancer within six years.

    Using this data, the team determined the overall cost-effectiveness of the program could be substantially increased if the health of the people being screened were to improve. Focusing on high-risk people could reduce the number of individuals who need to be screened by more than 80 per cent, the study suggests.

    The cost of screening was calculated to be $20,724 per year of life saved, a number considered to be cost-effective compared to the benchmark of $100,000 that is often paid for other cancer interventions in national healthcare.

    “Working with this team of investigators has driven the success of the study,” said Cressman. “The project arose from a strong multidisciplinary collaboration bringing together experts from across Canada who are passionate about public health and willing to invest their protected time in finding ways to optimize the way lung cancer care is delivered.”

    This research was predominantly funded by the Terry Fox Research Institute, the Partnership Against Cancer, and the Canadian Centre for Applied Research in Cancer Control.

    Click here to learn more about TFRI’s Pan-Canadian Early Lung Cancer Detection Study.

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    The study's lead author Sonya Cressman. 
  • One in two Canadians will get cancer, but research offers hope for cures

    by TFRI Admin | Jun 22, 2017

    Terry Fox

    Close to 50 per cent of all Canadians will be diagnosed with cancer in their lifetime. One in four Canadians will die of the disease. Around 60 per cent of high-priority cancer research projects were not funded in 2016.

    These sobering statistics were released by the Canadian Cancer Society on June 20 – but there’s good news too: survival rates have increased from 25 per cent in the 1940s to 60 percent today, a number both the Terry Fox Research Institute and the Terry Fox Foundation are determined to keep improving by investing in top-tier cancer research across the country and internationally.

    There has been tremendous success in increasing five-year survival rates for some cancers, such as thyroid (98%), testicular (96%), prostate (95%), melanoma (88%), female breast (87%) and Hodgkin lymphoma (85%). However survival rates for some cancers have remained stubbornly low, such as pancreatic (8%), lung and bronchus (17%), liver (19%), and brain (24%). These are the areas we are focusing on to find cures for all cancers.

    In 2016, the Terry Fox Research Institute and the Terry Fox Foundation invested $22.9 million dollars into research projects across the country with a focus on hard-to-treat cancers. These include: 

    Terry’s dream was to fund research to cure cancer, and he inspired us with that dream. We believe that it is through research that cures to cancer will be found, and survival rates for even the most challenging cancers will continue to increase.

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