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In a recent paper published March 2020 in Nature Cancer, research co-authored by Dr. Lorrie Kirshenbaum, Director of the Institute of Cardiovascular Sciences here at St. Boniface Hospital Research, shows how heart damage that often results from a widely employed cancer chemotherapy called doxorubicin can be prevented by a new experimental drug referred to as BAI1.

“It’s been well known for years that doxorubicin, a very effective component of regimens used to treat multiple cancers and leukemias in adults and children, has a serious downside of causing cardiac damage in some patients that can lead to eventual heart failure,” said Kirshenbaum. “Finding a way to prevent that damage while retaining doxorubicin’s anti-cancer benefits, is what drove this investigation.”

The work was five years in the making and was conducted in close collaboration with investigators Drs. Richard Kitsis and Evridipis Gavathiotis, Albert Einstein College of Medicine, New York (Download PDF): A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy. The work was also recently applauded by NIH’s National Cancer Institute website.

“Collaborations such as these can lead to major advancements and breakthroughs, and this is no exception” said Dr. Grant Pierce, Executive Director St. Boniface Hospital Research. “Our sincere congratulations to Dr. Kirshenbaum, Professor Department of Physiology & Pathophysiology, and Pharmacology & Therapeutics, University of Manitoba, and his associates on this work, which has the potential to save and extend many lives affected by breast cancer.”

The new study builds on insights from the investigators’ earlier research on cardiac damage by doxorubicin and the basic biology of a protein called BAX. Working through BAX, doxorubicin causes two different forms of cell death in the heart. BAI1 targets BAX to block both of these forms of cell death. Studies in animal models showed that BAI1 prevents heart failure from doxorubicin without interfering with the ability of doxorubicin to treat cancer. This work is important because it identified BAX as a single druggable target to prevent heart failure from doxorubicin. Further down the road, it may allow oncologists to prescribe higher doses of doxorubicin in combination with other cardiotoxic drugs, without causing heart damage.

With proof of concept now established, clinical trials will be initiated soon in the United States to test doxorubicin effects when administered in conjunction with BAI1.

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