August 25, 2020
OICR-supported researchers demonstrate new drug may eliminate triple negative breast cancer cells in certain patients, discover a new method to identify which patients will benefit
Adapted from UHN’s Media Release.
Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that often spreads to other organs and accounts for one in four breast cancer deaths. OICR-supported researchers at the University Health Network’s Princess Margaret Cancer Centre are zeroing in on the molecular mechanisms that fuel this deadly cancer’s runaway growth to develop more effective treatments for this disease.
In their study, recently published in Nature Communications, they found a promising approach that could potentially identify the patients who could benefit from a more precise, targeted therapy for TNBC.
“This disease has no precision medicine, so patients are treated with chemotherapy because we don’t have a defined therapeutic target,” says co-lead of the study Dr. Mathieu Lupien, Senior Scientist at the Princess Margaret Cancer Centre and OICR Investigator. “Initially, it works for some patients, but close to a quarter of patients recur within five years from diagnosis, and many develop chemotherapy-resistant tumours.”
“These savage statistics mean that we must improve our understanding of the molecular basis for this cancer’s development to discover effective, precise targets for drugs, and a companion test to identify which patients are most likely to benefit the most from such a therapy.”
The study investigated how TNBC cells are dependent on a specific protein called GLUT1 and its associated molecular pathways. Prior studies suggested that TNBC cells were dependent on GLUT1, but this study is the first to demonstrate that blocking GLUT1 function may be an effective therapeutic strategy for certain patients with TNBC.
Using a collection of cell lines, the researchers found that blocking this pathway with a drug-like chemical compound “starved” the cancer cells, but only in a subset of TNBC patient samples. The group investigated further and found a common trait between the cell lines that were sensitive to the drug – they had high levels of a protein called RB1. This indicates that patients with TNBC and high levels of RB1 may, one day, benefit from this drug.
“Having access to diverse cell models of triple-negative breast cancer allows us to distinguish where the potential drug will work, and where it won’t,” says Lupien. “Without this broad spectrum of samples, we might have missed the subset of triple-negative breast cancers that respond to our compound.”
Collectively, this study suggests that clinical evaluation of targeting GLUT1 in certain patients with TNBC is warranted.
“The more we understand about the molecular complexity of cancer cells, the more we can target with precision,” says co-lead of the study Dr. Cheryl Arrowsmith, Chief Scientist for the Structural Genomics Consortium Toronto laboratories and Professor of Medical Biophysics at the University of Toronto. “And the more we can build up a pharmacy of cancer drugs matched to specific changes in the cancer cell, the greater the chance of a cure.”
Read UHN’s Media Release.
February 7, 2019
Op-ed in The Globe and Mail hails innovation strategy that resulted in record-breaking investment by Celgene
In a contribution to The Globe and Mail titled “For Innovation, open science means business”, E. Richard Gold and Max Morgan point to the recent investment by U.S. pharmaceutical giant Celgene into a potential treatment for leukemia developed by OICR researchers, as an example of how Canada can successfully commercialize its scientific discoveries. The authors note that the uniquely Canadian approach employed by FACIT and OICR working together will, unlike other strategies, keep the intellectual property (IP) in Canada longer and see research and development, clinical trials and other outcomes, benefit Canada and Ontario.
Gold and Morgan point out that it was an open science collaboration between OICR and the University of Toronto’s Structural Genomics Consortium (SGC) that allowed for the initial scientific discovery behind the new potential drug to take place rapidly, since traditional concerns around IP weren’t a factor. This approach allowed FACIT and OICR to move towards targeted drug development much earlier than possible under other models, enabling them to create a patented drug candidate. Gold and Morgan call on Canadian governments to replicate the open science to IP model, which Celgene’s investment shows is a viable path to commercialization in Canada.
E. Richard Gold is James McGill professor, McGill Faculty of Law; senior fellow, Centre for International Governance Innovation; former technology lawyer. Max Morgan is chief policy officer and senior counsel, SGC; corporate secretary and legal consultant, M4K Pharma Inc. OICR has provided funding to M4K Pharma Inc. through its Cancer Therapeutics Innovation Pipeline initiative. SGC and OICR are long-term partners.
From the Globe and Mail (subscription required): For Innovation, open science means business
July 31, 2018
OICR-funded drug discovery project’s unique ‘open science’ business model is accelerating the search for a solution to lethal pediatric brain cancers
Diffuse intrinsic pontine glioma (DIPG) is a lethal and inoperable brain cancer with a median survival of less than a year from diagnosis. Finding solutions to this disease is challenging due to its rarity, scientific complexity and its presentation in pediatric populations. An OICR-funded team of researchers, led by Dr. Aled Edwards from M4K Pharma, have developed new potential drug candidates for DIPG that they will test in animal models in the coming months. They’ve reached this milestone ahead of schedule, with fewer resources required than anticipated, by using an ‘open drug discovery’ approach – sharing their methods and data with the greater research community to streamline the drug discovery process.
December 4, 2017
OICR launches groundbreaking Cancer Therapeutics Innovation Pipeline to drive cutting-edge therapies to the clinic
Ten new projects were selected in the pipeline’s inaugural funding round, highlighting Ontario’s strengths in collaboration and drug discovery.
Toronto (December 4, 2017) – The Ontario Institute for Cancer Research (OICR) today announced the Cancer Therapeutics Innovation Pipeline (CTIP) initiative and the first 10 projects selected in CTIP’s inaugural round of funding. CTIP aims to support the local translation of Ontario discoveries into therapies with the potential for improving the lives of cancer patients. The funding will create a new pipeline of promising drugs in development, and attract the partnerships and investment to the province necessary for further clinical development and testing.
“Ontario congratulates OICR on this innovative approach to driving the development of new cancer therapies,” says Reza Moridi, Ontario’s Minister of Research, Innovation and Science. “The Cancer Therapeutics Innovation Pipeline will help ensure that promising discoveries get the support they need to move from lab bench to commercialization, and get to patients faster.”
February 12, 2016
Doing things differently: The story behind the promising chemical probe developed by OICR and the Structural Genomics Consortium
A recent collaboration between researchers at OICR and the Structural Genomics Consortium (SGC) used a new open-source approach to early stage drug discovery to develop and share without restrictions a drug-like molecule (or chemical probe) called OICR-9429 in an effort to crowd-source cancer research. OICR-9429 specifically inhibits a protein called WDR5 and can be used to investigate its function in a cell.
“Testing a new cancer treatment takes significant time and resources and unfortunately many attempts fail late in the development process. Also, most of the research activities are carried out in parallel and without enough collaboration. This leads to the duplication of a great amount of effort and raises the cost of cancer drugs that do make it to the clinic,” explains Dr. Cheryl Arrowsmith, Chief Scientist at SGC Toronto.
September 3, 2015
The Ontario Institute for Cancer Research and the Structural Genomics Consortium develop and give away new drug-like molecule to help crowd-source cancer research
Through a novel open source approach the molecule has been made freely available to the cancer research community to help discover new therapeutic strategies for cancer patients sooner.
TORONTO, ON (September 3, 2015) – Researchers from the Ontario Institute for Cancer Research (OICR) and the Structural Genomics Consortium (SGC) at the MaRS Discovery District in Toronto have developed a new drug prototype called OICR-9429 and made it freely available to the research community. Already research conducted by international groups using OICR-9429 has shown it to be effective in stopping cancer cell growth in breast cancer cell lines and a specific subtype of leukemia cells.
Significant time and resources are required to test new cancer treatments but unfortunately most ideas fail late in the development process and most of the activities are carried out in parallel, without sufficient collaboration. This leads to massive duplication of effort and ultimately increased cost of cancer drugs. By making early stage drug-like compounds such as OICR-9429 available, OICR and the SGC are allowing researchers to more rapidly test new treatment strategies and facilitate sharing of the results. Independent studies from Philadelphia and Vienna have now shown that the cellular target of OICR-9429 may be relevant for drug discovery.
“In the time that it would normally take to negotiate a legal agreement to provide OICR-9429 to other research teams we have received results back from our collaborators showing that it can kill two different types of cancer cells,” says Dr. Cheryl Arrowsmith, Chief Scientist at SGC Toronto. “Opening our chemistry capabilities to the world’s scientists allowed us to crowdsource and accelerate the research.” Dr. Arrowsmith is also a Professor in the Department of Medical Biophysics, Faculty of Medicine at the University of Toronto and a Senior Scientist, Princess Margaret Cancer Centre, University Health Network.
“It is remarkable how quickly our research results were translated into discoveries by the groups around the world. This demonstrates that Ontario is a new hub of a global drug discovery effort,” says Dr. Rima Al-awar, Director and Senior Principal Investigator, Drug Discovery Program, OICR. “We are looking forward to seeing more research conducted with OICR-9429 and showing that this new approach to early-stage drug discovery has significant advantages.”
OICR-9429 works to inhibit a protein called WDR5 and two recent studies evaluated its effect on breast cancer and leukemia cell lines and returned encouraging results.
A study led by Dr. Shelly Berger at the University of Pennsylvania used OICR-9429 to stop cancer cell growth in a panel of breast cancer cell lines driven by mutated forms of the gene p53. In its normal form p53 is a tumour-suppressor, however once it is mutated it leads to a ‘gain of function’ and causes cancers to grow though its stimulation of WDR5 function. This research is significant as p53 is mutated in at least half of all cancers and is dysregulated in others.
A team headed by Drs. Florian Grebien and Giulio Superti-Furga at the CeMM Research Center for Molecular Medicine in Vienna, Austria used OICR-9429 to demonstrate the potential of WDR5 as a therapeutic target for leukemia. Their research showed that OICR-9429 stopped the growth of leukemia cells with a very specific mutation found in about nine per cent of patients with acute myeloid leukemia.
These two studies culminated in joint publications, in Nature and Nature Chemical Biology respectively, between the international researchers and the Ontario-based OICR and SGC teams.
“I applaud this innovative partnership between OICR and SGC and their collaborative efforts to catalyze cancer research worldwide,” says Reza Moridi, Ontario Minister of Research and Innovation. “Collaboration, both at home in Ontario and abroad, is key to driving scientific discoveries and ultimately delivering better care to cancer patients.”
OICR-9429 is just one in a series of drug-like compounds developed by the SGC that are enabling a new approach to early-stage drug discovery. The SGC and OICR teams are continuing their collaboration to identify additional drug-like molecules to advance cancer drug discovery.