Mystery Behind Heart Failure After Chemo Solved

Heat shock factor 1 protein identified as source of heart failure after chemotherapy

(RxWiki News) Scientists were working to find a drug target for heart muscle disease. Instead they incidentally discovered a key to preventing heart failure years after chemotherapy.

They found that blocking a cardiac protein called heat shock factor-1 (HSF-1) produced under stress-related factors could help prevent heart damage following treatment with common chemotherapy drug doxorubicin (Adriamycin.)

"Talk to an oncologist about the risks associated with chemotherapy."

Govindasamy Ilangovan, PhD, associate professor of internal medicine at Ohio State University and senior author of the study, noted that additional stress could be aggravating chemotherapy's effect on the heart. He said the results suggest that added stress could hurt the heart more than the actual chemotherapy.

During the study researchers used mice and cell cultures to identify HSF-1 as the source of chemotherapy-related heart damage known to be induced by stress -- such as by the chemo itself.

Two sets of mice received doxorubicin, including a set of mice that were genetically altered so that they were unable to produce HSF-1. Investigators found that the mice that did not have the protein had healthier hearts and lived longer following chemotherapy treatment.

The cell study revealed that when HSF-1 is blocked in the heart, it allows the activation of a gene producing a protein to pump the chemo drug out of the heart muscle cells to prevent them from dying. Unlike many other cell types, heart muscle cells cannot be regenerated. This muscle loss can reduce the heart's pumping ability, leading to heart failure.

"The drug Adriamycin has been a proven effective chemotherapy over the past several decades for multiple cancer types, including common cancers such as breast and lymphoma. The most serious, though uncommon, side effect of this drug is heart failure and it's related to cumulative dose of the drug," noted Patrick Maguire, MD, a radiation oncologist in North Carolina.

"A MUGA scan (to evaluate heart function) is usually ordered before treatment to ensure good baseline heart function, then drug dose is limited to minimize risk of heart failure. However, I'm unaware of preventative measures that can be taken otherwise."

Ilangovan and a team of researchers are using the findings to design drugs that could selectively inhibit HSF-1 in the heart. He envisions it as an additional therapy to protect the heart for cancer patients receiving chemotherapy.

Funded by grants from the National Institutes of Health, the study was recently published in journal Proceedings of the National Academy of Sciences.

Review Date: 
May 22, 2012