Tumours that originate in bone, muscle or connective tissues are called sarcomas. They are rare and account for only one per cent of malignancies. Sarcomas are compelling because of their size — they can be up to 30 centimetres in length and take up to 10 hours to remove — as well as their intimate and dangerous connection to the skeletal structure.
Doctors who perform sarcoma surgery need the fine motor skills of a pianist, the physicality of a carpenter and the coordinated approach of an engineer. This is a perfect description of Dr. Michael Monument, an orthopaedic oncology surgeon in Calgary.
“You remove the tumours with life-saving intent and reconstruct whatever is left behind,” explains the 38-year-old.
Monument had a childhood dream of becoming a professional hockey player, but his love of sciences made medicine a more suitable career path. He received his undergrad in cellular biology and genetics at the University of Calgary (U of C). After securing his medical degree and residency, also at the U of C, Monument travelled to the University of Utah to study sarcoma research and surgery through a three-year fellowship program. He has been in practice since 2014.
Monument is also an assistant professor. He teaches orthopaedic oncology courses, operating room procedures and small group anatomy to medical students and residents at the Cumming School of Medicine. He has a hip and knee replacement practice and leads a research team with a focus on the causes and treatment of sarcomas at the Cumming School of Medicine.
“I am busy,” he admits. “But I think if I was more efficient with my time, I could do more.”
One could argue this statement — Monument plays recreational hockey twice a week, is a long-distance runner and is in a committed relationship. He is also a gardener but is not totally feeling that love. “I am trying to test my green thumb out,” he says. “But I am having limited success so far.”
But challenges do not thwart him. In fact, they motivate him. His research is a case in point.
Monument is studying whether immunotherapy (a strategy used to boost the body’s natural immune function to treat cancer) might be useful in handling undifferentiated pleomorphic sarcoma (UPS), a.k.a. muscle-derived sarcoma. UPS is a high-grade, aggressive malignancy and the most common soft tissue sarcoma found in adults. Currently, there are no effective systemic therapies for UPS, and invasive surgery is usually recommended — this involves removing large amounts of tissue and, often, intricate reconstruction.
Immunotherapy is being used successfully in treating melanoma and lung cancers, so Monument was keen on exploring its viability for sarcomas.
For the last five years, he and his team of four core researchers have been engineering muscle sarcomas in mice, in an effort to best mimic a human tumour. A pathologist studies these engineered tissue samples and conducts genetic testing to determine which tumours are sufficiently similar to the human variety. Only up to 70 per cent meet the standard. The team then tracks the growth of the selected tumours, which are engineered to express fluorescent proteins with bio-luminescent components.
“You use a camera to look at them in live animals,” says Monument. “The cancer cells glow in the dark.”
At that point, the team injects a type of drug called a Stimulator of Interferon Genes (STING) receptor agonist directly into these tumours to disrupt blood flow and activate the cancer-killing properties of the immune system (this therapeutic strategy has already demonstrated such effects in other solid cancers). In their first pilot experiment, four out of six mice treated with a single STING dose had their tumours disappear within three months. Plus, efforts to re-activate the malignancies have failed.
“It is almost like they are now immune. This preliminary data is extremely exciting,” says Monument. He and his group are pioneering experimentation by injecting the STING agonist drug directly into sarcoma tumours — this category of therapy has never been attempted in sarcomas, specifically.
This year, Monument hopes to further his study by exploring the benefit of injecting more than one dose into the sarcoma tumours. He is also looking to test this therapeutic strategy on multiple different sarcoma subtypes. Will such attempts boost effectiveness, including keeping tumours from developing elsewhere? And what about the idea of sarcoma immunization — could the drug be used to prevent metastasis or to prevent sarcoma from recurring years down the road?
Answers to these questions could fundamentally alter the trajectory of the development of novel systemic therapies for sarcoma.
Many funding bodies are committed to this research. The Canadian Orthopaedic Foundation, the Alberta Cancer Foundation, the McCaig and Charbonneau Research Institutes with the Cumming School of Medicine and the Section of Orthopaedic Surgery at the U of C have provided a total of $300,000 to date.
“The long-term goal of this research is to use these [laboratory] experiments to see if STING agonist therapy is a viable therapeutic strategy for treating sarcomas, and in doing so justify building clinical trials looking at STING agonist therapy for human sarcoma patients who are metastatic or have little therapies available to them,” says Monument.
Colleagues are supportive and proud of Monument’s work and commitment to sarcoma advances and better outcomes for patients. “Mike is a rockstar because he can relate a message about research to many audiences — students, colleagues, researchers, patients and the lay public,” says Kevin Hildebrand, fellow orthopaedic surgeon and professor at the U of C. “He is passionate about his work and direction and connects well with people.”
For Monument, it is less about rockstar status and more about the big picture and the greater good. “As an orthopaedic surgeon, the challenge is to not simply look after the day-to-day clinical care of the patient, but to introduce novel ideas and generate high-quality research,” he says.
And to execute that passion and dedication in his hometown is a bonus, says Monument. “It is a privilege to work in Calgary.”
8 Questions with Dr. Monument
Describe what you do in 10 words or less.
I’m a musculoskeletal oncology surgeon and scientist.
What’s the biggest misperception about what you do?
The surgery is harder than the science.
Where do you get your best ideas?
Airplanes and road trips.
If you weren’t an orthopaedic surgeon, what would you be?
A professional hockey scout.
What’s the hardest lesson you’ve learned?
Balancing clinical, research and personal time is not easy.
What motivates you?
Being better today than I was yesterday.
What do you do to recharge?
Travel and ice hockey.
Why does your research matter?
Sarcoma patients desperately need new, effective therapies.