February 27, 2020
International research group finds leukemia drugs and other small molecules may shrink treatment-resistant lung tumours
Lung cancer is the leading cause of cancer death in Canada and around the world. These fatal cancers often arise as a patient’s tumour cells acquire new mutations and become resistant to treatment but Dr. Igor Stagljar has found a new way to stop these tumours. In fact, he may have found four.
Stagljar’s research group at the University of Toronto is well-known for developing a live drug screening method – named MaMTH-DS – that can test potential cancer-fighting molecules in living cells. In a recent study published in Nature Chemical Biology, he and collaborators used these methods to focus on a common mutation, dubbed C797S, which often arises in lung cancers just months after initial treatment. The group identified four new compounds that could block the effects of C797S mutations with no effect on healthy cells.
“Our new technology allows us to find molecules that could be used against cancers for which no other treatment options are available,” says Stagljar, who is a professor of molecular genetics and biochemistry at the University of Toronto. “The advantage of our method is that we are doing it in living cells, where we have all the other molecular machineries present that are important for signal transduction. Also, the compounds are fished at very low dose, which allows us to test for both permeability and toxicity at the same time.”
Conventional drug screening strategies were not able to detect these compounds but Dr. Stagljar’s approach brought these new promising molecules to light.Dr. Rima Al-awar
Two of the molecules identified have already been approved for patients with leukemia. Motivated by their recent findings, Stagljar and collaborators plan to evaluate the effects of these compounds in patients with lung cancer. The first clinical trial to evaluate one of these drugs – gilteritinib – is expected to launch later this year in Toronto, Canada and Zagreb, Croatia.
The other two molecules will require further research and development before they can be trialed in patients. One of these molecules, known as EMI1, could shut down the mutated cells in a completely new way, leveraging molecular machineries to degrade mutated proteins on the surface of tumour cells. The researchers think that EM1’s complex mechanism of action will make it more difficult for tumours to develop resistance to it.
Stagljar is working with Dr. Rima Al-awar, Head of Therapeutic Innovation and Drug Discovery at OICR, and her medicinal chemistry team to create an improved version of the EMI1 molecule. If proven successful, this molecule could potentially become a new treatment for the estimated 60,000 lung cancer patients worldwide who have the C797S mutation.
“Dr. Stagljar’s novel screening approach has identified these very promising molecules” says Al-awar. “We’re proud to collaborate with him and his group to further advance these molecules and accelerate the stages of experimentation between his discovery and helping those with the disease.”
Al-awar, whose drug discovery team recently brought a molecule for blood cancers into pre-clinical development, will leverage her group’s expertise to refine the molecule and move it into the next stage of development, where its ability to shrink tumours can be evaluated in experimental animal models and eventually patients.
This research was supported in part by the Consortium Québécois sur la Découverte du Médicament (CQDM), Cancer Research Society (CRS), Canadian Institute of Health Research (CIHR), Genome Canada and Ontario Research Fund. Stagljar was recently awarded a Prospects Oncology Fund grant from FACIT, OICR’s partner in commercialization, to develop a related drug screening platform, SIMPL.
This post has been adapted from the original announcement made by the University of Toronto Donnelly Centre.
November 1, 2019
Al-awar joins OICR’s executive team with plans to expand drug discovery and development initiatives across Ontario
Dr. Rima Al-awar has joined OICR’s executive team as Head, Therapeutic Innovation and Drug Discovery. In this role, she will lead one of OICR’s three key priority areas, Therapeutic Innovation, which focuses on validating novel cancer drug targets and advancing therapeutic candidates through pre-clinical development. She will continue leading OICR’s Drug Discovery Program and will build upon that team’s exceptional work in her new position.
Here she discusses her new role and her plans to grow OICR’s Therapeutic Innovation platform.
What does this promotion mean for you and your team?
Since joining OICR, I have spent several years building an experienced and talented team that I’m very proud of. We have developed great assets and established fruitful partnerships with collaborators and industry partners. We have a very rich and promising portfolio of potential new cancer therapeutics.
I believe we are in a great position to expand and capitalize on our successes. My new position will allow me to take a strategic role in therapeutic innovation at OICR so that we can enable future successes both here, in Toronto, and across the province. I need to think of creative and strategic funding models, how best to strengthen the platform’s structure and establish additional synergistic partnerships in the community. In the long run, this means advancing more projects into development.
How will this new role allow you to do that?
I’ll have a seat at the table in strategic conversations with our executive team. I’ll bring a unique perspective with my expertise in drug discovery and development, and I look forward to representing Therapeutic Innovation, an important part of OICR.
In this role I will also help ensure that resources are allocated to the most promising projects. I’m a big proponent of focusing on select projects and doing them well and in a timely and competitive fashion as opposed to stretching our resources across too many projects, which often ends up slowing progress. In this position, I believe I can do that more effectively.
How does this new appointment differ from your previous position as Director of Drug Discovery?
I will still be leading the Drug Discovery team, but I’ll be relying on leaders within the team to take on some of my previous day-to-day responsibilities, and in turn, they will delegate some of their current responsibilities. I see this role as an opportunity to strengthen the Drug Discovery team and encourage the pace of career development within the team.
Within the scope of my new role, we are going to have to think creatively about progressing additional projects forward faster, which will mean harnessing new technologies and recruiting new expertise in different scientific disciplines.
When it comes to collaborations, I expect that my role will be just as collaborative as it was before. My goal is to continue to strengthen our current collaborations and forge new ones. We can’t bring new therapeutics to patients on our own.
What can we expect to see over the next year?
I want to explore the idea of expanding our breadth of collaborations to include biologics, immunotherapies, and novel drug delivery methods, technologies and models that impact drug discovery. I will be travelling to different research institutes across the province and outside of Ontario to look for more opportunities. The goal of this effort would be to identify and build on strengths in the community. We’re looking to enable and facilitate new, promising projects in areas of unmet needs. Expanding our network across Ontario is very important. We have built a strong foundation, we have deep expertise, a rich portfolio and now we are going to take it to the next level. I look forward to encouraging more synergy across our organization and Ontario.
August 22, 2018
Ratheesh Subramaniam talks about his work in OICR’s Drug Discovery team and how it could help doctors make a difference in treating cancer patients.
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.”
July 12, 2017
Given the advancements in treating many other types of cancer, it may come as a surprise that outcomes for patients with the most deadly form of ovarian cancer have not improved in 50 years. This form, known as High Grade Serous Ovarian Cancer (HGSOC), accounts for 80 per cent of ovarian cancer deaths in Canada. Surgery and chemotherapy can be effective, but ultimately three-quarters of women with HGSOC will see their disease return. To deliver better outcomes for patients, OICR has launched a new ‘all star team’ of ovarian cancer researchers.
February 10, 2017
The quest for a new cancer drug often begins when a protein target is implicated as an important driver in tumourigenesis. For cancer researchers, small molecules that block or stimulate such proteins can be valuable tools in research. Not only do they help us understand the role that the protein plays in cancer biology, but they also enable researchers to demonstrate which tumours are sensitive toward inhibition or stimulation with that protein target of interest, providing early clues as for patient selection and biomarker identification. Moreover, the knowledge that a small molecule can bind to such a protein builds confidence that this target is indeed “druggable,” which can provide a powerful stimulus to initiate a sustained effort to find medicines for that target.