March 8, 2019
OICR’s Drug Discovery team and Princess Margaret Cancer Centre researchers collaborate to turn a research discovery into a potential cancer breakthrough
For more than three decades, researchers have tried to develop drugs that target the MYC oncoprotein – a protein that can contribute to half of all cancers – but traditional approaches to blocking MYC have not been successful. The structure of the MYC protein makes it ‘undruggable’; it cannot be blocked by a small molecule or a drug, so new strategies to inhibit the activity of this protein are needed.
Dr. Linda Penn, Senior Scientist at the Princess Margaret Cancer Centre, recently discovered a new way of preventing MYC from promoting cancer growth by stopping the interaction between the MYC protein and a ‘druggable’ partner protein, G9a.
“We investigated MYC and discovered G9a as a key partner protein. We blocked G9a using both genetic and pharmacological strategies. We saw that inhibiting G9a using an inducible knockdown strategy had the potential to melt tumour cells away,” says Penn. “But for some reason, no matter what we tried, we didn’t see the tumour-fighting effect of the G9a compound inhibitor in animal models. Something didn’t line up.”
A discovery like Penn’s, however, can only be brought to patients if it can first be demonstrated in living experimental models, also known as in vivo. The results of Penn’s in vivo experiments were inconclusive, preventing her from publishing her promising findings in a top-tier journal and advancing this line of research.
Navigating the preclinical minefield
The compound – or molecule – that Penn’s team was using to block G9a in vitro wasn’t doing the same in vivo and they didn’t understand why. Lacking the medicinal chemistry expertise needed to solve this problem, Penn turned to OICR’s Drug Discovery group.
“All of Dr. Penn’s experiments and all of the published literature implies that the compound should have worked, but unfortunately that wasn’t her observation,” says Dr. Ahmed Aman, Principal Research Scientist in the Drug Discovery group at OICR. “We had to break this problem down and solve it methodically while considering the various factors that could have contributed to these results.”
The Drug Discovery team evaluated the compound and found that it didn’t have the drug-like properties necessary to demonstrate activity in vivo. More specifically, they discovered that the compound would break down in the body before having a chance to inhibit G9a. Although the compound that they tested would not be useable as a drug, Penn’s study was now conclusive. Finding the missing piece of the puzzle allowed her team to publish their discovery in Cancer Cell and proceed with identifying and investigating new compounds to target G9a more effectively.
Collaboration to translation
Penn says that she worked with the Drug Discovery group because of their stellar reputation in the industry, strong track record and unique expertise.
“Without the Drug Discovery team, I really don’t know where I would have gone,” says Penn. “I simply didn’t have established relationships with medicinal and analytical chemists nor private industry to help me solve these chemistry problems.”
Together, Penn and the Drug Discovery group are continuing to investigate G9a and how to block it from interacting with the MYC protein. They are using another reported G9a inhibitor, which has been prepared in-house by the Drug Discovery team that Aman says should be able to work much more effectively in vivo.
“Our collaboration with the Penn group is a great example of how we hope to leverage our drug discovery capabilities to support investigators across Ontario and advance their research efforts,” says Dr. Rima Al-awar, Director and Senior Principal Investigator of OICR’s Drug Discovery group.
Learn more about OICR’s Drug Discovery services and capabilities through the Collaborative Research Resources directory.
October 16, 2018
OICR offers new CT calibration service as part of its Collaborative Research Resources portfolio
Using imaging devices to help make treatment decisions in the clinic requires rigorous testing, quality assurance and routine calibration of the imaging machinery. These standards are especially important when the imaging technology is novel or unique, such as in the case of perfusion imaging – a relatively new technique used to diagnose a cancer’s stage by showing how blood flows through the tumour.
October 16, 2018
Kelly McDonald talks about her work at the Ontario Heath Study and how the data provided by participants is now helping researchers in Canada and around the world.
September 6, 2017
OICR’s Tissue Portal is a new central entry and exit point for human tissue derived samples handled at OICR. This will serve as a gateway for tissue-based research projects to access over 100 services and resources at OICR being made available through the OICR Collaborative Research Resources on a cost-sharing basis. The Tissue Portal will standardize and streamline the storage, processing and distribution of samples for collaborative research studies at OICR.
March 29, 2017
Polymerase chain reactions (PCR) are one of the most common tools used in molecular biology labs worldwide. This technique allows researchers to amplify, or increase, the amount of DNA in a sample so that they have more to work with. To keep track of the original molecules from a sample, chemical ‘barcodes’ are added. While barcodes serve an important purpose they can lead to errors and interfere with results. To prevent these cross-reactions a small team of international researchers have devised an ingenious method to ‘hide’ the barcodes when needed, leading to increased sensitivity and more reliable results.
Continue reading – New approach improves sensitivity of DNA sequencing, producing more reliable results
October 27, 2016
Ilinca Lungu, a Research Technician in OICR’s Transformative Pathology Program, talks about her group’s contributions to recent findings from the PanCuRx Translational Research Initiative.
Access to the Transformative Pathology Program’s resources and expertise is available to the research community through Diagnostic Development in OICR’s Collaborative Research Resources Directory. For more information about how you can access these services, visit oicr.on.ca/collaborative-research-resources.
September 19, 2016
Dr. Rebecca Tamarchak discusses the launch of OICR’s new Collaborative Research Resources Directory, how it works, and plans for its development in the future.
Over the past decade, OICR has established state-of-the-art Technology Programs in molecular pathology and diagnostic development, genomics, informatics, medicinal chemistry and imaging, which are translating promising cancer discoveries into products, services and policies that improve cancer prevention and care for patients.
July 26, 2016
OICR is making its technology infrastructure, expertise and resources more available to the Ontario cancer community
Technology platforms are often one of the biggest enablers of high-impact research. Since it was established in 2005, OICR has invested in developing technology infrastructure, expertise and resources in diagnostic development, genomics, imaging, informatics and medicinal chemistry. These clusters consist of research and technical experts and state-of-the-art equipment.