Study suggests newer breast cancer drug may protect heart

Jun 08, 2007

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

Explore further: Lilly psoriasis drug fares well in late-stage test

add to favorites email to friend print save as pdf

Related Stories

Straight to the heart

Aug 18, 2014

A battery-less, wirelessly-powered implantable defibrillator for atrial fibrillation is being developed by an international team of researchers in the UK, Venezuela and the US. With the ability to sense the ...

Venom gets good buzz as potential cancer-fighter

Aug 11, 2014

Bee, snake or scorpion venom could form the basis of a new generation of cancer-fighting drugs, scientists will report here today. They have devised a method for targeting venom proteins specifically to malignant cells while ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Muscle-powered bio-bots walk on command (w/ Video)

Jun 30, 2014

(Phys.org) —A new generation of miniature biological robots is flexing its muscle. Engineers at the University of Illinois at Urbana-Champaign demonstrated a class of walking "bio-bots" powered by muscle ...

Designing exascale computers

Jul 23, 2014

"Imagine a heart surgeon operating to repair a blocked coronary artery. Someday soon, the surgeon might run a detailed computer simulation of blood flowing through the patient's arteries, showing how millions ...

Recommended for you

Lilly psoriasis drug fares well in late-stage test

2 hours ago

Drugmaker Eli Lilly and Co. said its potential psoriasis treatment fared better than both a fake drug and a competitor's product during late-stage testing on patients with the most common form of the skin disease.

New US restrictions on painkiller to take effect

15 hours ago

The federal government is finalizing new restrictions on hundreds of medicines containing hydrocodone, the highly addictive painkiller that has grown into the most widely prescribed drug in the U.S.

Boxed warnings are common in novel therapeutics

Aug 19, 2014

(HealthDay)—Boxed warnings are common on recent drug approvals, and many occur years after approval, according to a research letter published online Aug. 15 in JAMA Internal Medicine.

User comments : 0