Researchers Identify Link Between Herceptin and Cardiac Failure

Researchers at the Salk Institute have identified the probable link between the breast cancer drug Herceptin and cardiac failure, a common side effect of the treatment.

Herceptin targets the HER2 protein, which is over abundant in some breast cancers. New findings show that, in mice, erbB2 (the mouse version of HER2) is needed for heart cells to function properly.

"It was possible that Herceptin triggered cardiac malfunction by a number of mechanisms, but now it appears to be that the drug's direct action on erbB2 is the culprit," said Kuo-Fen Lee, associate professor and senior author of the study published in Nature Medicine.

It should be possible to develop new generations of drugs that can provide the benefits of Herceptin while minimizing harmful effects on heart function, said Lee.

"To do that we need to know more about the role of erbB2 in both cancer and heart cells," he added.

Researchers engineered mice that would stop making erbB2 selectively in their heart tissue. Hearts from the mice, examined at one to six months of age, showed clear signs of cardiomyopathy similar to those seen in Herceptin-related cardiac dysfunction.

"This mouse model will help us identify new mechanisms to protect patients from Herceptin cardiomyopathy, and thereby allow more aggressive and early use of Herceptin for a broad range of human cancers," said Ken Chien, director of the Institute of Molecular Medicine at the University of California, San Diego and co-author of the study.

Because all women taking Herceptin are also given other anti-cancer drugs including anthracyclines, and that therapy tends to increase cardiac dysfunction in patients, researchers also studied the effects of anthracyclines on the erbB2 mutant mice.

The loss of erbB2 function caused by Herceptin makes cardiac muscle more susceptible to anthracycline toxicity, reported Lee.

"These results suggest it may be appropriate to examine alternative chemotherapeutic agents in combination with Herceptin, in order to avoid the increased risk of heart disease associated with combined Herceptin/anthracycline therapy," said Lee.

Researchers are focusing their efforts on developing agents that can stimulate the heart, allowing the use of Herceptin aggressively while protecting the heart.

Other sources: Salk Institute