Emily WilliamsChemotherapy can save a life, but for many cancer survivors, the treatment can also leave behind unexpected damage. One of the most serious complications is chemotherapy-induced cardiotoxicity, a form of heart injury that can lead to long-term cardiac dysfunction or even heart failure.
A new University of Alberta study led by associate professor and Co-associate Chair of Research for the faculty of medicine and dentistry Gopinath Sutendra is helping explain why some patients are more vulnerable than others, and how the tumour itself may be playing a hidden role.
Sutendra’s path into this field of research started long before this study.
“I did my PhD in a cardiovascular lab studying heart failure due to various stimuli,” he said. “Then during my postdoc fellowship in Oxford, I moved into cancer biology.”
As he transitioned between the two fields, he noticed a troubling gap. Cancer patients were increasingly surviving their disease only to develop heart failure and very little research connected these two outcomes.
“At the time, there was a gap,” he said. “Cardiologists were giving treatments without understanding the cancer environment, and cancer people were not understanding the complexities of the heart. We needed to integrate both together and study this clinical problem in the appropriate model.”
This sparked a question that would shape the next decade of his work: beyond chemotherapy itself, could the tumour also influence the heart?
His team’s recent findings suggest that it can. By analyzing blood samples from the MANTICORE clinical trial, the researchers identified tumour-secreted factors including molecules like inosine and hypoxanthine that circulate through the bloodstream and weaken the heart’s defenses.
These molecules bind to receptors in heart muscle cells and make them more susceptible to damage from chemotherapy drugs that are designed to disrupt DNA replication.
U of A research team seeks to refine cancer treatments
“Everyone was thinking, we know chemotherapy can have an effect on the heart,” Sutendra said. “But we asked, can the tumour make the heart more receptive to chemotherapy? And this was an unanswered question.”
Once they identified the tumour-secreted factors, the team traced them back to the protein that produces them, a synthesizer called Zenin F2A1. Sutendra explained why it immediately stood out as a promising therapeutic target.
“It is a synthesizer for the tumour-secreting factor that makes the heart more susceptible to cardiotoxicity, and it is also essential for tumours to grow and metastasize,” he said. “This was an ideal target because we knew that it would protect the heart but at the same time have a good benefit against the tumour.”
The team has already developed a drug that inhibits this protein. Early results in pre-clinical cancer and heart failure models have shown promise.
“We know at this point that it is safe and tolerable in pre-clinical models and is effective at decreasing tumour growth and protecting the heart,” he said.
The next step is to study the drug in large animal models, specifically swine models, to assess safety and toxicology.
“These are unpublished papers that are submitted and we are expecting the first batch in the next three to four months,” he added.
In the future, these findings could help oncologists tailor treatments more precisely. Sutendra imagines a scenario where two patients with the same cancer receive different recommendations based on their tumour’s environment.
“Based on the serum we can get an idea of the tumour environment,” he explained. “We can give more advice on personalized care, maybe slightly different therapies or advice on lifestyle, exercise or nutrition, to tackle the tumour and protect the heart. It is a holistic approach.”
Research team’s goal is “to make cancer treatment not only effective, but safe”
The study’s implications may even extend beyond cancer treatment. The mechanism uncovered by studies of tumour to heart communication could open new doors for regenerating heart cells damaged by heart attacks or heart failure.
“If someone gets a heart attack or heart failure and they lose heart cells, can we use knowledge from these pathways to replenish these heart cells that may be lost? Yes, this can be helpful.”
Despite the scientific complexity of the field, what motivates Sutendra is not only the possibility of new treatments but the process of discovery itself.
“As a basic science researcher, what excites most of us is the discovery,” he said. “At the beginning we do not know the implications, but by acquiring that knowledge we can use it for good, for better treatments and diagnostics.”
He also highlighted the dedication of trainees who helped drive the project forward.
“The first author of this paper was a graduate student who had a lot of data to go through, interpretation, long nights, and this is the value of that work,” he said. “He discovered something with the team that will hopefully lead to better treatments and diagnostics for others.”
For now, the team is working toward a future where life-saving cancer therapies no longer come with a hidden cost to the heart.
“The goal,” Sutendra emphasized, “is to make cancer treatment not only effective, but safe, so patients can survive and live long, healthy lives.”
