A research team at the University of Alberta may have discovered how to block chemotherapy’s harmful impacts on the heart while making the treatment more effective at the same time.
“As the survival of cancer patients is increasing, we are observing an increased incidence of heart failure in these patients. Therefore, new and effective treatments are desperately needed to prevent the development of this condition,” said Gopinath Sutendra, U of A professor and Alberta Innovates cardio-oncology translational health chairman.
Sutendra is one of two leads on the research team.
Chemotherapy is an effective drug treatment for cancer, but its deadly attack on cancer cells often leaves other cells in the body damaged, such as the heart. Since cells in the heart take longer to regenerate than cells in other organs, heart damage is nearly irreversible, Sutendra said.
This has been a known issue for a long time, which propelled researchers at the University of Alberta to find a solution.
The team compared the environment of the heart to the location of a tumour and noticed a stark difference between the two. While the heart is in an oxygen-rich zone, tumours tend to lie in oxygen-poor places.
This notable difference helped the team target the heart, since it has more proteins that could be modified.
“This differential — or opposing — regulation of cell death between heart and tumour cells is a highly novel and potentially selective treatment against chemotherapy-mediated cardiac dysfunction,” Sutendra explained.
The team discovered proteins oxidize (a process that requires oxygen) at a higher rate in the heart, since there’s more oxygen flowing in the environment. By metabolizing lung tumours in mice the same way, they found chemotherapy treatments to be more effective.
It also blocked the drug's harmful impacts on the heart.
Researchers used a popular chemotherapy pill in the trials, which is known to cause cardiac issues in patients. The findings mean patients being treated for cancer could potentially need fewer dosages of chemotherapy.
“If you're making a therapy more effective, you can theoretically lower the dose, which would reduce other side effects as well in the patient,” said Bruno Saleme, co-lead on the research project and first author of the study.
Their findings were published Feb. 6 as a cover story in Science Translational Medicine. Saleme said they hope their work will lead to clinical trials using other drugs that stabilize proteins the same way.
Sutendra said the findings could also lead to discoveries among other forms of heart failure, which is the next step for researchers. They’ll also be examining whether protein stabilization has the same impact on other organs in the body.
“We are very excited about the potential impact this work may have in overall cancer patient care,” he said.
The three-year study was supported with funding from the Canadian Institutes of Health Research, the Heart and Stroke Foundation and the Alberta Innovates Translational Health Chair in Cardio-Oncology.