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Connect the DOX

Researcher finds connection between cancer drug and heart health

Dr. Lorrie Kirshenbaum, Principal Investigator, Cardiac Gene Biology, Institute of Cardiovascular Sciences at St-Boniface Hospital Research

Dr. Lorrie Kirshenbaum, Principal Investigator, Cardiac Gene Biology,
Institute of Cardiovascular Sciences at St-Boniface Hospital Research

Doxorubicin – or DOX, for short – is an effective anti-cancer drug that has been prescribed for about a quarter of a century. It’s most often used in the treatment of leukemias and lymphomas, as well as breast, uterine, ovarian, bladder, and lung cancers.

But that effectiveness comes with a significant side effect – a high incidence of heart failure. Dr. Lorrie Kirshenbaum has discovered the source of the side effect, and is well on the way to confirming a way to combat it.

“What happens is that Doxorubicin turns on a gene called Bnip3, and when Bnip3 is turned on, it’s a killer,” says Dr. Kirshenbaum, Principal Investigator, Cardiac Gene Biology, Institute of Cardiovascular Sciences at St-Boniface Hospital Research. “It is the same gene that gets turned on when someone has a heart attack. Heart cells die, they don’t grow back, and congestive heart failure ultimately takes hold.”

So while DOX reliably kills cancer cells, it also triggers an effect that kills heart cells. The evidence is robust. There are even data that show that people who receive DOX in childhood show a greater likelihood of having heart failure much later in life.

Dr. Kirshenbaum, who is also a Professor of Physiology and a Canada Research Chair in Molecular Cardiology at the University of Manitoba, was the lead author of a recent paper that described the Bnip3 phenomenon. It is a major discovery that could improve the lives of cancer patients taking DOX.

Now with the mechanism understood, Dr. Kirshenbaum and his colleagues are working to solve the problem.

“Our goal is to find a way to prevent Bnip3 from being turned on by DOX,” says Dr. Kirshenbaum. “I think we’re about five years away, but I believe we will develop an ‘inhibitor’ drug that can be taken with DOX to keep the Bnip3 gene dormant in the heart without compromising the drug’s ability to kill the cancer cells.”

Because of the prevalence of DOX, many people stand to benefit. “This is exciting because the road to developing the inhibitor points to a new line of research,” says Dr. Kirshenbaum. “We’ve been studying the role of Bnip3 in heart failure for a long time which put us in a position to make the DOX discovery. The whole experience speaks to the progression of science and how your own work, and the work of others, can lead to really important findings.”

Dr. Kirshenbaum and his team are grateful to St-Boniface Hospital Foundation and its donors for their role in the research. “The support of the Foundation has been instrumental in helping us to make progress in our work,” says Dr. Kirshenbaum. “Generosity makes discovery possible.”

This article was originally published in the Spring 2015 edition of Believe

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