Study suggests newer breast cancer drug may protect heart

By uncovering how one breast cancer drug protects the heart and another does not, Duke University Medical Center researchers believe they may have opened up a new way to screen drugs for possible heart-related side effects and to develop new drugs.

The Duke researches compared the actions of two breast cancer drugs in experiments involving human cells and rats. The drugs in question were the older drug trastuzumab, whose trade name is Herceptin, and the newer drug lapatinib, whose trade name is Tykerb.

The results of the study appear early online in the journal Proceedings of the National Academy of Science.

The main side effect of trastuzumab is that it can damage heart muscle cells. Heart abnormalities have been detected in 2 to 7 percent of women taking the drug, and about one in ten women cannot take the drug because preexisting heart problems put them at greater risk for heart damage. To date, there appear to be fewer cardiac effects associated with lapatinib therapy.

Both drugs are prescribed to women whose cancerous breast cells have HER2 genes that are overactive. Approximately one in four women with breast cancer have this overactive gene, which is associated with increased cancer recurrence and worse outcomes. Lapatinib was approved earlier in March for use in women who have not responded to trastuzumab therapy.

“Trastuzumab revolutionized the treatment of HER2-positive breast cancers and represents an effective therapy for some women with one of the most aggressive forms of breast cancer,” said Duke oncologist Neil Spector, M.D., first author of the paper.. “However, now we have two agents that go after the same target and both have an effect against the cancer, but one appears to have a greater potential – based on this preliminary work – for causing cardiovascular damage.

“It is important to be clear that we are reporting findings from pre-clinical experiments, so while they suggest a difference between these two agents, it would be over-interpreting the study to conclude that women taking trastuzumab should consider any treatment change,” Spector said. “However, it may be important to conduct well-controlled clinical trials to answer this question.”

In addition to its association with breast cancer, HER2 is also essential for the early development and later sustenance of heart muscle cells. It appears that trastuzumab’s mechanism for blocking HER2 is different.

“We found that lapatinib activates a critical pathway that protects heart cells from ‘committing suicide’ as a result of stress,” Spector continued. “Heart muscle cells require a tremendous amount of energy to function properly and are therefore extremely sensitive to energy deprivation as a consequence of reduced oxygen or nutrient supply. In addition, heart muscle cells appear to be sensitive to the death promoting effects of inflammation.

“Our experiments in isolated human heart muscle cells indicate that lapatinib activates a pathway that protects cardiac muscle cells from the death-promoting effects of mediators of inflammation, which are activated in cancer patients, particularly those who have received chemotherapies that damage heart tissue,” Spector said. “In contrast, trastuzumab does not activate this protective pathway.”

With clinical trials currently investigating the combination of lapatinib with trastuzumab, there is a possibility that the effects of lapatinib in cardiac muscle cells might protect the heart against potential toxicity associated with trastuzumab, Spector added.

More broadly, Spector said that these findings of how lapatinib bestows cardiovascular protection during times of stress – whether from chemotherapy or heart muscle cells deprived of oxygen during a heart attack -- could be used in other situations.

“Using this system, we could theoretically screen drugs that are in the development phase to see what their effects may be on heart muscle cells,” Spector said. “We may be able to select the drug candidates that have the fewest cardiovascular side effects and theoretically would be safer for patients. This way, we could find out about some of these potential problems long before the drugs even make it to market.”

Additionally, Spector said there is the potential for the development of similar drugs that can be used as protective agents in situations where the heart is stressed for periods of time, such as during heart attacks, coronary artery bypass surgery or angioplasty. Such a drug could even be used to preserve cardiac function in hearts being harvested for transplant, he said.

Source: Duke University Medical Center

Related stories:

Fat-regenerating 'stem cells' found in mice
Researchers have identified stem cells with the capacity to build fat, according to a report in the October 17th issue of the journal Cell, a Cell Press publication. Although they have yet to show that the cells can renew themselves, transplants of the progenitor cells isolated from the fat tissue of normal mice can restore normal fat tissue in animals that are otherwise lacking it.
Vitamin D a key player in overall health of several body organs, says UC Riverside biochemist
Essential for life in higher animals, vitamin D, once linked to only bone diseases such as rickets and osteoporosis, is now recognized as a major player in contributing to overall human health, emphasizes UC Riverside's Anthony Norman, an international expert on vitamin D.
A fine balance
Once a toddler has mastered the art of walking, it seems to come naturally for the rest of her life. But walking and running require a high degree of coordination between the left and right sides of the body. Now researchers at the Salk Institute for Biological Studies have shown how a class of spinal cord neurons, known as V3 neurons, makes sure that one side of the body doesn't get ahead of the other.
Can stem cells heal damaged hearts? No easy answers, but some signs of hope
Recent studies indicate that infusing hearts with stem cells taken from bone marrow could improve cardiac function after myocardial infarction (tissue damage that results from a heart attack). But in a recent systematic review, Cochrane Researchers concluded that more clinical trials are needed to assess the effectiveness of stem cell therapies for heart patients, as well as studies to establish how these treatments work.
Novel imaging approach may assist in predicting success of treatment for atrial fibrillation
University of Utah researchers have developed a magnetic resonance imaging (MRI)-based method for detecting and quantifying injury to the wall of the heart's left atrium in patients who have undergone a procedure to treat atrial fibrillation. The results of the study are published in the Oct. 7, 2008, issue of the Journal of the American College of Cardiology.
Mayo Clinic discovery may help diabetic gastric problem
Mayo Clinic researchers have found what may provide a solution to one of the more troubling complications of diabetes -- delayed gastric emptying or gastroparesis. The researchers showed in animal models that a red blood cell derivative increases production of a key molecule, normalizing the digestive process. The findings appear in the current online issue of the journal Gastroenterology (http://www.gastrojournal.org/).
Scientists trace extensive networks regulating alternative RNA splicing
RNA targets of tissue-specific splicing factors Fox-1 and Fox-2 are successfully predicted
Two professors at Cold Spring Harbor Laboratory (CSHL) have succeeded in tracing intricate biochemical networks involving a class of proteins that enable genes to express themselves in specific tissues at particular moments in development.
New class of hormone from 'healthy fat cells' benefits body metabolism in mice
(PhysOrg.com) -- Scientists at the Harvard School of Public Health (HSPH) have identified in mice a newly discovered class of hormones -- lipokines. In tomorrow's issue of the journal Cell they report that lipokine is a molecule in mice that helps stop, or even reverses obesity-related conditions such as insulin resistance and "fatty liver."

News discussion:

Medicine & Health news