U of A research aims to protect heart during chemo
Chemotherapy may become more effective and less harmful to the heart thanks to research at the University of Alberta.
Researchers have long known that the aggressive attack on cancer cells from chemotherapy often causes damage to other cells in the body, including the heart, making patients more prone to develop heart problems down the road.
This is what inspired Gopinath Sutendra, U of A professor and Alberta Innovates cardio-oncology translational health chairman, to research possible solutions.
“This is the first targeted therapy at the preclinical level to actually prevent the side-effects of
chemotherapy on the heart and simultaneously enhance tumour regression,” Sutendra said.
Chemotherapy is especially problematic for the heart because cells there regenerate slower than in other organs, Sutendra said, making damage nearly irreversible.
While the heart resides in an oxygen-rich environment, a tumour resides in an oxygen-poor environment, so the U of A research team thought this could be a way to target the heart because it contains more proteins that could be modified.
“When (the protein) was tagged by oxygen in the heart, it actually preserved cardiac function when we treated the heart with chemotherapy agents,” Sutendra said.
Stabilizing a metabolic protein the same way in a lung tumour, chemotherapy treatment was more effective.
The team used mice for its research, with human lung cancers and a common chemotherapy medication in pill form known to cause cardiac dysfunction in patients.
“That protein was preferentially tagged in the heart compared to the tumour where it wasn’t tagged by oxygen, and this somehow changed the structure of the protein such that it was preventing the chemotherapy-mediated
cardiac dysfunction in the heart,” Sutendra said.
Researchers hope the findings will soon be able to be tested in clinical trials with similar drugs that stabilize the protein — pyruvate kinase M2 (PKM2) — with many already being tested in clinical trials for other diseases.
“We’re reaching out to pharmaceutical companies that have some of these compounds that they’re using in other diseases,” Sutendra said. “There is interest there to test those ones in our model because then they can be moved to the clinical trial more easily.”
These findings could have similar
implications for other forms of heart failure, Sutendra said, which will be the next area of study for the team.
The effectiveness of a similar approach in other organs of the body is another potential area of research following this discovery.
The study, published Wednesday as a cover story in Science Translational Medicine, was supported by funding from the Canadian Institutes of Health Research, the Heart and Stroke Foundation and the Alberta Innovates Translational Health Chair in Cardio- Oncology.