How his work has improved the lives of cancer patients in Saskatchewan
By Nikki Desjardins for SHRF
Supporting early career researchers with novel ideas is one objective of Saskatchewan Health Research Foundation’s (SHRF) Establishment grant program. This type of support can be the key to encouraging the next big thing in health innovation. That was the case when Dr. Humphrey Fonge from the University of Saskatchewan received his Establishment grant in 2015.
His research is in the broad field of nuclear medicine science but is specifically focused in oncology and the development of what are called theranostic agents. Theranostics are compounds or molecules that have a diagnostic component as well as a therapeutic component. These molecules, whether diagnostic or therapeutic, are able to precisely target very specific biomarkers/proteins on cancer cells that are distinguishing factors of different types of cancers.
Fonge’s SHRF Establishment grant proposed a very novel approach to designing these types of molecules for breast cancer. His Establishment grant proposed to develop theranostic agents against epidermal growth factor receptor III (HER3) positive breast cancer. HER3 is a protein on breast cancer cells and is the frequent cause of resistance to therapeutics that target HER2 positive breast cancer, such Herceptin®. His therapeutic approach was to develop highly specific antibody constructs against HER3 protein that carry multiple very potent cytotoxic compounds – compounds that kill cancer cells. A diagnostic antibody construct is also developed that would allow physicians to accurately select patients that would benefit from the therapy.
Directly related to his SHRF grant, Fonge has been able to move one compound into a phase one clinical trial in the area of diagnostics. The promise of this diagnostic compound is the fact that it will help physicians more accurately select patients who may benefit from a particular drug that targets biomarkers in the cancer.
Currently, the gold standard for diagnosing cancer is pathology. Pathology relies on taking a sample of a lesion or tumour. This can be invasive and only provides a snapshot of the disease because you can only sample one lesion at one particular point in time. In many cases, there may be thousands of lesions in the body. With the diagnostic approach using the compound developed in Fonge’s lab, you will be able to scan every lesion in the body of the patient with one imaging procedure, giving physicians a full picture and understanding of the disease.
On the therapeutic side of Fonge’s work, which he hopes will be moving into a phase one clinical trial in the next 18-24 months, is the potential for more effective treatments. For example, if a breast cancer patient is HER2 positive, meaning they overexpress a particular biomarker or protein, they are treated with a drug (e.g. Herceptin® or and/other HER2 targeted drug) that about 70% of patients develop a resistance to. This new molecule, which has seen positive results in animal models, hopes to widen the therapeutic window, meaning improved potency and reduced side effects, with the hopes of more patients seeing the benefits of treatment.
The nature of Fonge’s work is bench to bedside, meaning his lab is involved in every stage of drug development. They develop the molecules, testing them in different models, from basic things like tissue cultures to more advanced things like different animal models of disease. Once the molecules are fully validated in animals, they try to move them into clinical trials which takes significant funding and collaborations.
Thinking back to starting his lab without even a microscope, Fonge credits his SHRF Establishment grant as the funding source that allowed him to stay within in his niche area of research and set up his lab to do the work that needed to be done. With his SHRF funding, he was also able to recruit a talented postdoctoral fellow to help with the proof of concept information needed to obtain further grants from other funding sources.
“My SHRF grant allowed me to develop the platform technology that I keep applying on different cancer types and different biomarkers and that keeps me going,” says Fonge. “The positive reviews my Establishment grant proposal received gave me the confidence and a form of validation to move the work very aggressively.”
Since coming to the University of Saskatchewan seven years ago, Fonge has developed collaborations with basic researchers, clinicians and even industry partners who play a role in the development of molecules or in designing clinical trials with the end goal of advancing patient outcomes and care.
“The research ecosystem here may be small, but I think it’s just incredible,” comments Fonge. “Here I am able to do basic research. I’m able to produce a clinical grade drug. Then, within walking distance, I can go for coffee with some of the physicians and design clinical trials. This is something a lot of people would take for granted and it doesn’t exist in many places in the world.”
Since receiving his Establishment grant, Fonge has been able to extend his work to other cancer types, notably prostate, lung, colorectal and neuroendocrine tumors. This has been made possible with major grants such as a nearly $2M combined in Project Scheme grant funding over the past two years from the Canadian Institutes of Health Research, and $1.8M from Western Economic Diversification and Innovation Saskatchewan for clinical translation of targeted biologic molecular imaging agents, among other smaller grants from organizations like the Sylvia Fedoruk Centre and Canadian Breast Cancer Foundation.
Unrelated to his grants, but instead an extension of his work motivated by letters he receives from patients, is his commitment to working with his colleagues and the province to bring clinical trials that have drastic implications for patient care to Saskatchewan.
“I think the people of this province deserve to have diagnosis or therapeutic options that I see others enjoying in the States or Europe,” comments Fonge.
It’s this commitment to his work and the outcomes he has been able to achieve that spurred his recognition with SHRF’s 2020 Impact Award at their annual Santé Awards presented online on December 3. The Impact Award recognizes one past Establishment grant recipient for their contributions to building capacity, advancing health research knowledge, informing decision making and contributing to health and socioeconomic impacts.
“I am truly grateful for my SHRF Establishment grant,” says Fonge. “It really allowed me to set my own research program and that has had a ripple effect.”