"At the clinical level, we've known for some time that heart dysfunction from chemotherapy is a major issue, but at the scientific level, we've only recently begun to look at signalling pathways that may be implicated in this condition," said Gopi Sutendra, Alberta Innovates Translational Health Chair in Cardio-Oncology at the U of A.
"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."
The heart resides in an oxygen-rich environment, compared to a tumour which resides in an oxygen-poor environment.
The team found that the oxidation of proteins--a process that requires oxygen--was preferentially increased in the heart. By stabilizing a specific metabolic protein called pyruvate kinase M2 (PKM2)--also preferentially oxidized in the heart--with a drug compound, the researchers completely prevented heart damage from the chemotherapy, and enhanced the potency of the chemotherapy against lung tumours in preclinical mouse models.