January 20, 2020
OICR researchers identify novel causes of cancer progression in the non-coding genome, opening new lines of investigation for several cancer types
Toronto – (January 20, 2020) In an unprecedented pan-cancer analysis of whole genomes, researchers at the Ontario Institute for Cancer Research (OICR) have discovered new regions of non-coding DNA that, when altered, may lead to cancer growth and progression.
The study, recently published in Molecular Cell, reveals novel mechanisms of disease progression that could lead to new avenues of research and ultimately to better diagnostic tests and precision therapies.
Although previous studies have focused on the two per cent of the genome that codes for proteins, known as genes, this study analyzed mutation patterns within the vast non-coding regions of human DNA that control how and when genes are activated.
We found evidence of new molecular mechanisms that may cause cancer and give rise to more-aggressive tumours.
“Cancer-driver mutations are relatively rare in these large non-coding regions that often lie far from genes, presenting major challenges for systematic data analysis,” says Dr. Jüri Reimand, investigator at OICR and lead author of the study. “Powered by novel statistical tools and whole genome sequencing data from more than 1,800 patients, we found evidence of new molecular mechanisms that may cause cancer and give rise to more-aggressive tumours.”
The research group analyzed more than 100,000 sections of each patient’s genome, focusing on the often-overlooked non-coding regions that interact with genes through the three-dimensional genome. One of the 30 key regions discovered was predicted to have a significant role in regulating a known anti-tumour gene in cancer cells, despite being more than 250,000 base pairs away from the gene in the genome. The group performed CRISPR-Cas9 genome editing and functional experiments in human cell lines to explore the cancer-driving properties of this non-coding region.
“We characterized several non-coding regions potentially involved in oncogenesis, but we’ve just scratched the surface,” says Reimand. “With our algorithms and the rapidly growing datasets of patient cancer genomes and epigenetic profiles, we look forward to enabling future discoveries that could lead to new ways to predict how a patient’s cancer will progress and ultimately new ways to target a patient’s disease or diagnose it more precisely.”
Reimand’s research group developed the statistical methods behind this study and made them freely available for the research community to use. These methods have been rigorously tested against other algorithms from around the world.
We’ve shown that our method, called ActiveDriverWGS, can excavate these regions and pinpoint specific areas that are important to cancer growth.
“Looking into the non-coding genome is really important because these vast sections regulate our genes and can switch them on and off. Mutations in these regions can cause these regulatory switches to act abnormally and potentially cause – or advance – cancer,” says Helen Zhu, student at OICR and co-first author of the study. “We’ve shown that our method, called ActiveDriverWGS, can excavate these regions and pinpoint specific areas that are important to cancer growth.”
“Although these candidate driver mutations are rare, we now have the first experimental evidence that one of the mutated regions regulates cancer genes and pathways in human cell lines,” says Dr. Liis Uusküla-Reimand, Research Associate at The Hospital for Sick Children (SickKids) and co-first author of the study. “As the research community collects more data, we plan to look deeper into these regions to understand how the mutations alter gene regulation and chromatin architecture in specific cancer types to enable the development of new precision therapies to patients with these diseases.”
This study was supported by OICR through funding provided by the Government of Ontario, and by the Canadian Institutes of Health Research (CIHR), the Cancer Research Society (CRS), the Estonian Research Council, and the Natural Sciences and Engineering Research Council of Canada (NSERC).
Whole genome sequencing data used in this study was made available by the International Cancer Genome Consortium’s Pan-cancer Analysis of Whole Genomes Project (ICGC PCAWG), also known as the PCAWG Project or the Pan-Cancer Project.
January 13, 2020
Researchers identify five subtypes of pancreatic cancer, uncovering new opportunities for targeted treatment of the aggressive disease
Toronto – (January 13, 2020) Researchers at the Ontario Institute for Cancer Research (OICR) and the University Health Network (UHN) have discovered detailed new information about the subtypes of pancreatic cancer. A better understanding of the disease groups may lead to new treatment options and improved clinical outcomes for this lethal disease.
The study, published today in Nature Genetics, represents the most comprehensive analysis of the molecular subtypes of pancreatic cancer to date. Through detailed genomic and transcriptomic analyses, the research group identified five distinct subtypes of the disease (Basal-like-A, Basal-like-B, Classical-A, Classical-B, and Hybrid) with unique molecular properties that could be targeted with novel chemotherapies, biologics and immunotherapies.
“Therapy development for pancreatic cancer has been hindered by an incomplete knowledge of the molecular subtypes of this deadly disease,” says lead author Dr. Faiyaz Notta, Co-Leader of OICR’s Pancreatic Cancer Translational Research Initiative (PanCuRx) and Scientist at UHN’s Princess Margaret Cancer Centre. “By rigorously analyzing advanced pancreatic cancers – which is the stage of disease that most patients have when they’re diagnosed – we were able to create a framework. This will help us develop better predictive models of disease progression that can assist in personalizing treatment decisions and lead to new targeted therapies.”
The study is based on data from more than 300 patients with both early stage and advanced pancreatic cancer who participated in COMPASS, a first-of-its-kind clinical trial that is breaking new ground in discovery science and personalized pancreatic cancer treatment. COMPASS is enabled by advanced pathology laboratory techniques at UHN and OICR, and next generation sequencing at OICR.
“Most pancreatic cancer research is focused solely on early stage – or resectable – tumours, but in reality, pancreatic cancer is often found in patients after it has advanced and spread to other organs,” says Notta. “COMPASS allowed us to look into these advanced cancers while treating these patients, develop a better understanding of the biology behind metastatic pancreatic cancer, and shed light on the mechanisms driving disease progression.”
Interestingly, the Basal-like-A subtype, which had been difficult to observe before this study, was linked with a specific genetic abnormality. Most of the Basal-like-A tumours harboured several copies of a mutated KRAS gene, also known as a genetic amplification of mutant KRAS. The research group hypothesizes that some of the subtypes arise from specific genetic changes that occur as pancreatic cancer develops.
“This research opens new doors for therapeutic development,” says Dr. Steven Gallinger, Co-Leader of OICR’s PanCuRx, Surgical Oncologist at UHN and Senior Investigator, Lunenfeld Tanenbaum Research Institute at Mount Sinai Hospital. “We look forward to capitalizing on the promise of these discoveries, building on our understanding of pancreatic cancer subtypes, and bringing new treatments to patients with the disease.”
This research was supported by OICR through funding provided by the Government of Ontario, and by the Wallace McCain Centre for Pancreatic Cancer by the Princess Margaret Cancer Foundation, the Terry Fox Research Institute, the Canadian Cancer Society Research Institute, the Pancreatic Cancer Canada Foundation, the Canadian Friends of the Hebrew University and the Cancer Research Society (no. 23383).
November 6, 2019
FACIT launches assessment of venture philanthropy models to scale Canadian commercialization of cancer research
Ms. Donna Parr and Dr. Niclas Stiernholm recruited to broaden public/private equity expertise
TORONTO, ON (November 6, 2019) – FACIT, a commercialization venture venture firm, reported on the expansion of its Executive-in-Residence program and new strategic initiatives. Ontario is home to world-leading cancer research connected through the collaboration model established by the Ontario Institute for Cancer Research (OICR), FACIT’s strategic partner. Growing market signals suggest Canadian philanthropy, oncologists and patients want more discoveries translated into therapies and technologies that directly impact cancer care, while also supporting Canadian entrepreneurialism. Commercialization of innovations is aligned with OICR’s translational mission and a strategic imperative for the province’s university and research hospital partners.Continue reading – FACIT launches assessment of venture philanthropy models to scale Canadian commercialization of cancer research
October 30, 2019
Next generation liquid biopsy platform to revolutionize companion diagnostics
TORONTO, ON (October 30, 2019) – FACIT, a commercialization venture group, together with the University of Toronto (“U of T”), announced the creation of Ontario-based Cellular Analytics (the “Company”). Cellular Analytics is founded upon a proprietary microfluidic platform that enables molecular characterization of cancer at the level of single circulating tumour cells. The technology quantitatively detects sensitivity to immune-oncology agents ‘on-chip’ at both significantly lower sample volumes and at a fraction of the cost. Seed capital from FACIT’s Compass Rose Oncology Fund will be used to develop the non-invasive, commercial prototype of the Company’s lead product. This critical capital also allows Cellular Analytics to maintain its momentum and continue strategic discussions with potential partners and investors to attract follow-on financing.
The platform, with an initial application in lung cancer, was discovered at the U of T lab of Dr. Shana Kelley. The professor and serial entrepreneur will act as the Chief Scientific Officer of Cellular Analytics. “Dr. Kelley’s technology is rapid, exquisitely accurate and inexpensive, which positions the Company well for clinical application across a range of cancers and competing in the diagnostics market,” said Dr. David O’Neill, President, FACIT. “Partnering with the University of Toronto on exciting new biotechnology companies like Cellular Analytics is aligned with FACIT and OICR’s joint strategy to support entrepreneurship and translate the benefits of research to patients and the Ontario economy.”Continue reading – FACIT and University of Toronto launch precision medicine company: Cellular Analytics
October 9, 2019
Change in just one letter of DNA code in a gene conserved through generations of evolution can cause multiple types of cancer
Toronto – (October 9, 2019) An Ontario-led research group has discovered a novel cancer-driving mutation in the vast non-coding regions of the human cancer genome, also known as the “dark matter” of human cancer DNA.
The mutation, as described in two related studies published in Nature on October 9, 2019, represents a new potential therapeutic target for several types of cancer including brain, liver and blood cancer. This target could be used to develop novel treatments for patients with these difficult-to-treat diseases.
“Non-coding DNA, which makes up 98 per cent of the genome, is notoriously difficult to study and is often overlooked since it does not code for proteins,” says Dr. Lincoln Stein, co-lead of the studies and Head of Adaptive Oncology at the Ontario Institute for Cancer Research (OICR). “By carefully analyzing these regions, we have discovered a change in one letter of the DNA code that can drive multiple types of cancer. In turn, we’ve found a new cancer mechanism that we can target to tackle the disease.”Continue reading – Researchers discover a new cancer-driving mutation in the “dark matter” of the cancer genome
September 26, 2019
FACIT’s Prospects Oncology Fund invests in Ontario-developed medical device and novel therapeutic platform technologies
Niche early-stage investment program seeds Ontario’s developing pipeline of oncology assets
TORONTO, ON (September 26, 2019) – Three promising Ontario-based oncology innovations are recipients of seed capital through the latest round of FACIT’s Prospects Oncology Fund. Medical device start-up Xpan Inc., Dr. Igor Stagljar of the University of Toronto, and the Drug Discovery Program at the Ontario Institute for Cancer Research (OICR) were selected to receive seed funding among a top-tier pool of applicants.
Xpan Inc., whose CEO Zaid Atto also won FACIT’s Falcons’ Fortunes pitch competition earlier this year, is developing expandable surgical access ports that aim to increase safety and efficiency of minimally invasive surgeries. Dr. Stagljar is developing a unique and disruptive system for detecting protein-protein interactions in real time for drug discovery applications, while OICR’s Drug Discovery Program, led by Dr. Rima Al-awar, will receive funds towards the development of a platform targeting multiple members of the WD40 repeat domain (WDR) family with small molecules. The lattermost project builds on OICR and FACIT’s recent success in executing a $1B USD strategic transaction with Celgene for a related WDR5 asset.Continue reading – FACIT’s Prospects Oncology Fund invests in Ontario-developed medical device and novel therapeutic platform technologies
July 3, 2019
Bridges built between Israel and Canada thanks to philanthropic donation from Joseph and Wolf Lebovic
TORONTO (July 3, 2019) – The Ontario Institute for Cancer Research (OICR), the Institute for Medical Research Israel-Canada (IMRIC) at the Hebrew University of Jerusalem and the Canadian Friends of Hebrew University (CFHU) today honour the successful conclusion of the first round of the Joseph and Wolf Lebovic Cancer Genomics and Immunity Fellowship Program, a cross-continent multidisciplinary collaboration between experts in cancer research. The Program forged two new partnerships between labs in Canada and Israel and provided a unique training opportunity for early career researchers in both countries. These collaborations led to the development of a new potential cancer-killing virus and a new drug candidate for leukemia.
Fellowships were awarded to Adrian Pelin from the lab of Dr. John Bell at The Ottawa Hospital Research Institute, in Ottawa, Ontario and Yoav Charpak Amikam from the lab of Dr. Ofer Mandelboim at IMRIC in Jerusalem, Israel. The collaboration improved the specificity and immune-triggering abilities of the potential oncolytic Vaccinia virus.
Another pair of fellowships were awarded to Dr. Laura Garcia-Prat from the lab of Dr. John Dick at the Princess Margaret Cancer Centre, in Toronto, Ontario and Waleed Minzel and Eric Hung from the lab of Dr. Yinon Ben-Neriah at IMRIC. This partnership enabled the development of leukemia xenograft models to help validate the efficacy of a new drug candidate, as recently published in the scientific journal Cell.
The Lebovic Fellowship Program was established by a philanthropic donation provided to IMRIC by Joseph and Wolf Lebovic – two brothers who survived the Holocaust, immigrated to Canada and have recently been appointed as Members of the Order of Canada for their contributions to the Toronto community.
“We’d like to congratulate the fellows today on their progress which was made possible by the generous support of Joseph and Wolf Lebovic. The funding provided by the Lebovic brothers allowed us to create a platform for Ontario scientists to establish collaborations with researchers in Israel and we look forward to strengthening this platform for future collaborative work,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR.
“We congratulate the fellows today on their achievements during this first round of the program. IMRIC is proud to continue our collaboration with an institute as distinguished as OICR, supported by the inspiring philanthropy of Joseph and Wolf Lebovic,” says Prof. Haya Lorberboum-Galski, Chairman of IMRIC. “We feel that this collaboration between top Canadian and Israeli researchers will surely lead to significant and game-changing advances in the world arena.”
“Thanks to the vision and generosity of Joseph and Wolf Lebovic, they have been instrumental in creating an international collaboration that will continue to strengthen Israel-Canada connections while benefitting humankind,” says Rami Kleinmann, CEO and President of Canadian Friends of Hebrew University. “CFHU is grateful for their continuing and dedicated support.”Continue reading – Bridges built between Israel and Canada thanks to philanthropic donation from Joseph and Wolf Lebovic
April 9, 2019
Entrepreneurs from Ontario’s Nanology Labs and Xpan Inc. receive FACIT investment for early-stage cancer innovations
Latest recipients slated to accelerate Ontario’s commercialization momentum are a 2018 finalist and 2019’s winner of FACIT’s Falcons’ Fortunes pitch competition
TORONTO, ON (April 8, 2019) – FACIT, an Ontario First business accelerator and investor for oncology innovations, is pleased to announce recent successes in its mission to help bridge the capital gap often experienced by early-stage entrepreneurs. The newest recipient of FACIT’s Prospects Oncology Fund is Nanology Labs, a start-up based out of the University of Toronto.
Nanology has developed an innovative low toxicity MRI contrast agent that circumvents the limitations of other MRI contrast agents currently available. This exciting nanoparticulate system leverages manganese to illuminate early stage tumours, including those in the brain, in a manner that allows clinicians to make better treatment decisions. Concurrently, it produces oxygen molecules in the tumour which enhances therapeutic efficacy of irradiation. “This seed funding is critical in enabling our technology to reach its next inflection point, moving our system closer to the clinic and positioning our company for further investment,” said Dr. Mohammad Ali Amini, CEO and Co-Founder of Nanology. “We were fortunate to have been chosen as a finalist in FACIT’s 2018 pitch competition, which helped to strengthen our subsequent application to the Prospects Fund.”Continue reading – Entrepreneurs from Ontario’s Nanology Labs and Xpan Inc. receive FACIT investment for early-stage cancer innovations
January 29, 2019
TORONTO (January 29, 2019) – A first-of-its-kind therapy for leukemia discovered by researchers in the Ontario Institute for Cancer Research’s (OICR) Drug Discovery Program, and under preclinical development, has attracted investment from Celgene Corporation that could exceed US$1 billion – which would make it the largest transaction to date for a preclinical asset discovered in Canada.
This investment will allow for clinical trials based in Ontario, and will further research and development of the drug and other cancer research innovations developed in the province. The commercialization of this technology was conducted by OICR’s strategic partner FACIT and demonstrates the realization of the two partners’ long-term vision of creating a sustainable pathway for therapeutic innovation in Ontario.
“The progress of this pre-clinical drug towards the clinic is an example of how OICR, working with its partners, is accelerating cancer research in Ontario and increasing investment so that new innovations can help patients as soon as possible,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “Today’s announcement shows how OICR and FACIT’s unique model for research and commercialization can generate long-term impact for the province of Ontario.”
The project is built on the observation that a protein known as MLL-1 plays an important role in promoting the development of leukemia. It does this through binding with a partner protein called WDR5. This new therapy works by disrupting the MLL-1/WDR5 protein-protein interaction, therefore inhibiting the cancer-promoting activity of the MLL-1 protein.
The possibility of targeting WDR5 to disrupt the cancer-driving activity of MLL-1 was first suggested by one of OICR’s partners, the Structural Genomics Consortium (SGC) at the University of Toronto, where researchers saw its potential and proposed a collaboration with OICR’s Drug Discovery (DD) program. OICR DD and SGC researchers worked together to develop an active and selective WDR5 “chemical probe” that could be used to test the anti-leukemia hypothesis. After OICR and SGC scientists demonstrated this probe could disrupt the interaction of WDR5 and MLL-1 in cells, they shared the compound with academic investigators in Ontario and around the world, who showed the probe could stop the growth of leukemia and other cancer cells.
Once the probe was in the public domain, the OICR DD group seized the opportunity to leverage its expertise to improve the drug-like properties and potency of the probe, while creating novel intellectual property, in order to fully realize its therapeutic and commercial potential. This subsequent development of the pre-clinical drug by OICR DD was made possible by their extensive experience in the pharmaceutical industry and academia, a unique model that has helped to develop assets that are solid candidates for investment and further development by industry partners. OICR DD is one of the only industry-academic hybrid drug discovery teams in Ontario.Continue reading – New potential treatment for leukemia discovered by OICR scientists draws major industry investment
January 14, 2019
Landmark pan-cancer study analyzes mutation signatures of low oxygen in more than 8,000 tumours
TORONTO (January 14, 2019) – Unlike healthy tissues, tumours thrive in low-oxygen environments, often acquiring the ability to resist treatment and spread to other sites in the body. Despite being a well-known cause of therapy resistance and metastasis, the impact of low oxygen, known as hypoxia, on tumour cells is poorly understood. As reported today in Nature Genetics, researchers have discovered molecular hallmarks of hypoxia in the first-ever pan-cancer analysis of low oxygen in human tumours, with a special focus on prostate cancer.
The study investigated more than 8,000 human tumours across 19 different cancer types, including prostate tumours from the Canadian Prostate Cancer Genome Network (CPC-GENE). The authors discovered common markers of hypoxia that could help predict cancer aggressiveness and inform treatment decisions.Continue reading – Researchers discover common markers of tumour hypoxia across 19 cancer types
September 13, 2018
Prospects Oncology Fund seeds developing pipeline of Ontario-based biotech innovations
TORONTO, ON (September 13, 2018) – With an expanding portfolio of breakthrough innovations, FACIT is committed to supporting Ontario entrepreneurs through the latest round of its Prospects Oncology Fund. FACIT has selected three novel cancer therapeutic discoveries to receive early-stage capital – biotechnology start-up Talon Pharmaceuticals (“Talon”), the Drug Discovery team at the Ontario Institute for Cancer Research (“OICR”) and CCRM. The Prospects Fund provides entrepreneurial scientists with the capital resources necessary to achieve critical proof-of-principle studies for their cutting-edge breakthroughs aiming to benefit future patients.
September 11, 2018
OICR’s Genome Informatics team plays key role in development of the Gabriella Miller Kids First Data Resource Portal
Toronto (September 11, 2018) – Today, the Gabriella Miller Kids First Data Resource Center (DRC) at the Children’s Hospital of Philadelphia launched the Kids First Data Resource Portal, which will advance personalized medicine for the detection, therapy, and management of childhood cancer and structural birth defects. As the Kids First DRC’s chief outward-facing tool, the Kids First Data Resource Portal serves the needs of a diverse group of patients, researchers, and clinicians partnering to create the world’s largest database of pediatric genomic data, and provides the necessary tools and computational resources for their analysis and interpretation.