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.”
The research group discovered that the mutation, termed the U1-snRNA mutation, could disrupt normal RNA splicing and thereby alter the transcription of cancer-driving genes. These molecular mechanisms represent new ways to treat cancers carrying the mutation. One of the potential treatment approaches includes repurposing existing drugs, which, by bypassing early drug development stages, could be brought into the clinic at an accelerated rate.
“Our unexpected discovery uncovered an entirely new way to target these cancers that are tremendously difficult to treat and have high mortality rates,” says Dr. Michael Taylor, Paediatric Neurosurgeon, Senior Scientist in Developmental and Stem Cell Biology and Garron Family Chair in Childhood Cancer Research at The Hospital for Sick Children (SickKids) and co-lead of the studies. “We’ve found that with one ‘typo’ in the DNA code, the resultant cancers have hundreds of mutant proteins that we might be able to target using currently available immunotherapies.”
The U1-snRNA mutation was found in patient tumours with certain subtypes of brain cancer, including nearly all of the studied samples from adult patients with sonic hedgehog medulloblastoma. The mutation was also found in samples of chronic lymphocytic leukemia (CLL) – the most common type of adult leukemia – and hepatocellular carcinoma – the most common type of liver cancer.
“This discovery is an example of how OICR is working together with partners in Ontario and across the world to support cutting-edge research that can be used in the development of precision therapies for cancer patients worldwide,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR.
The two related publications – one which focused on brain cancer and the other on CLL and liver cancer – were both led by researchers in Ontario, including Dr. Michael Taylor, who is also a Professor in the Departments of Surgery and Laboratory Medicine and Pathobiology at the University of Toronto, and Dr. Lincoln Stein at OICR. Both of the studies involved international collaborators including Dr. Xose Puente at the University of Oviedo, Dr. Elias Campo at the Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) and the Universitat de Barcelona and others.
The studies were powered in part by data from the OICR-led Pan-Cancer Analysis of Whole Genomes (PCAWG) project, one of the largest coordinated cancer research endeavors to date that analyzed more than 2,800 cancer whole genomes from the International Cancer Genome Consortium (ICGC).
This research was supported in part by a Translational Research Initiative grant from OICR through funding provided by the Government of Ontario. This work was also funded in part by Genome Canada and SickKids Foundation.
About the Ontario Institute for Cancer Research (OICR)
OICR is a collaborative, not-for-profit research institute funded by the Government of Ontario. We conduct and enable high-impact translational cancer research to accelerate the development of discoveries for patients around the world while maximizing the economic benefit of this research for the people of Ontario. For more information visit www.oicr.on.ca.
About The Hospital for Sick
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is a founding member of Kids Health Alliance, a network of partners working to create a high quality, consistent and coordinated approach to paediatric health care that is centred around children, youth and their families. SickKids is proud of its vision for Healthier Children. A Better World.
Ontario Institute for Cancer Research
The Hospital for Sick Children (SickKids)
416-813-7654 ext. 201436
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.
July 11, 2018
New funding for the Canadian Cancer Clinical Trials Network will help more cancer patients access clinical trials
Toronto (July 11, 2018) – The Ontario Institute for Cancer Research (OICR) and the Canadian Partnership Against Cancer (the Partnership) today announced renewed funding for the Canadian Cancer Clinical Trials Network (3CTN). The funding will ensure Canada remains a world leader in academic cancer clinical trials, help to increase opportunities for patients to receive promising new treatments and continue to improve outcomes for cancer patients through research.
June 27, 2018
World-leading genomics cloud computing group builds clinical tool for cancer care in Ontario
TORONTO, ON (June 27, 2018) – Ziliomics Inc., a start-up created by FACIT, received seed financing from the Prospects Oncology Fund. Derived from a leading oncology bio-computing group and leveraging insights from the world’s largest cancer genomics projects, Ziliomics develops web-based, modular software platforms that help physicians make actionable treatment decisions for patients living with cancer. Together with FACIT’s interim executive management model, the capital advances the development of Heliotrope, Ziliomics’ lead software product, and positions the company for corporate partnerships and additional financing. Financing terms were not disclosed.
June 13, 2018
Entrepreneur adds US oncology management experience to Ontario commercialization
TORONTO, ON (June 13, 2018) — The Board of Trustees announced the appointment of David O’Neill as the President of FACIT. Dr O’Neill joined FACIT in 2013 as Vice President, Business Development, bringing cancer drug development expertise as well as an extensive business network in pharma and biotech. As Acting President for the last year, he has elevated the profile of the organization and enabled FACIT to continue to deliver critical commercialization financing to innovative start-ups in the growing Ontario market.
May 1, 2018
Ontario Institute for Cancer Research welcomes new President and Scientific Director, Dr. Laszlo Radvanyi
Toronto (May 1, 2018) – Mr. Tom Closson, Chair of the Ontario Institute for Cancer Research’s (OICR) Board of Directors, today welcomed to the Institute Dr. Laszlo Radvanyi, OICR’s new President and Scientific Director. Radvanyi was selected after an extensive international search and has extensive oncology-related experience from his time spent in industry, with a particular focus in immuno-oncology. Radvanyi will work with the Ontario cancer research community, and OICR’s commercialization partner FACIT, to see that Ontario’s best innovations are reaching cancer patients as quickly as possible.
Radvanyi joins OICR from EMD Serono (Merck KGaA, Darmstadt Germany), where he was a Senior Vice President, Global Senior Scientific Advisor in Immunology and Immuno-Oncology. There he played a central scientific advisory role, facilitating major academic centre alliances and ran EMD Serono’s CAR T-cell program, in partnership with Intrexon. He also served as Global Head of the Immuno-Oncology Translational Innovation Platform, where he was instrumental in rebuilding immuno-oncology research at the company, hiring new world-class scientific staff, as well as pruning and re-orienting the discovery pipeline.