Updated on June 12, 2022
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THURSDAY, March 15, 2007 (HealthDay News) -- Drugs commonly used to control high blood pressure may also shrink lung tumors, new animal studies show.
As prescribed, the medicines -- known as angiotensin-converting enzyme (ACE) inhibitors -- keep blood pressure in check by boosting levels of the "angiotensin (1-7)" hormone, thereby prompting dilation of blood vessel walls.
Blood pressure patients taking ACE inhibitors also have lower rates of lung cancer, noted a team from Wake Forest University School of Medicine in Winston-Salem, N.C.
Investigating further, they found that angiotensin (1-7) cuts back on levels of cycloxygenase-2 (cox-2), an enzyme that promotes cell growth and is often elevated in lung cancer patients.
In the team's latest experiment, boosting angiotensin (1-7) levels in mice shrank lung cancer tumors by 30 percent.
"We are cautiously optimistic, but you know how these things go," said study co-author Patricia E. Gallagher, a researcher at Wake Forest's hypertension and vascular research center. "So many of these drugs go to trial, and while they work great in animals, when you get to the patient population, they're just not as effective. But to this point, we can say that, in mice, we got a reduction in cox-2 and a big reduction in tumor size without any toxic side effects."
The findings are reported in the March 15 issue of Cancer Research.
According to the American Cancer Society, lung cancer remains the leading cause of cancer death among men and women, killing more Americans than colon, breast, and prostate cancer combined. Because they are typically diagnosed at a later stage of disease, 6 in 10 lung cancer patients will die within the first year following diagnosis. Five-year survival is just 14 percent, and an estimated 170,000 Americans die each year from the disease.
In their study, the Gallagher team worked with a group of two- to four-week-old mice that had received transplanted lung cancer cells derived from a 58-year-old patient. The tumors were allowed to grow for 32 days.
Rather than testing ACE inhibitors themselves, the researchers injected half the mice with the angiotensin (1-7) hormone for a 28-day treatment period. The remaining mice received saline.
The experiment stimulated blood levels of angiotensin (1-7) in the mice to concentrations equivalent to those found in humans being treated with ACE inhibitors.
Subsequent dissections revealed that cox-2 levels diminished significantly in the treated mice, while lung tumors shrank by 30 percent. In contrast, tumors in mice receiving the saline solution grew to 2.5 times their pre-treatment size.
Gallagher and her colleagues uncovered no evidence of toxic side effects among the angiotensin (1-7) mice. The rodents displayed no apparent changes in body weight, heart rate or blood pressure, the researchers said.
They pointed out that negative side effects are a big concern, given that a class of drugs known as cox-2 inhibitors (which include Celebrex and the now-banned Vioxx and Bextra) have also been shown to reduce lung cancer risk. However, studies suggest that those drugs may carry an increased risk for cardiovascular complications such as heart attack, angina and stroke.
The authors said further study was needed to establish if higher doses of angiotensin (1-7) might be tolerated, or whether longer treatment periods might promote even more tumor reduction.
Gallagher said human trials are set to begin within two weeks. She added that if the current findings pan out, hormone-boosting drugs such as ACE inhibitors could ultimately play a significant role in lung cancer care, either as a stand-alone intervention or as part of a multi-pronged effort to combat the disease.
"One thing, too, we're hoping, is that we'll be able to apply these drugs in combination with other current therapies, so we can reduce the amount of chemotherapies being used," she said, "because, of course, chemotherapy has such toxic side effects. So, maybe in a combined cocktail, we'll be able to really improve people's quality of life."
Gallagher stressed that even if the drugs only moderately enhance lung cancer survival that would still be a major advance.
"Even if everyone in the world who smoked stopped today, we'd still have lung cancer patients for decades, because it's a slow-growing disease," she said. "So, if this would work and reduce people's cancer or even give them an extra two years of life, that means a lot to somebody. When you've got cancer, every little bit helps."
Dr. Bartolome R. Celli, professor of medicine at Tufts University and the chief of pulmonary care at St. Elizabeth's Medical Center in Boston, was similarly optimistic.
"The rate of mortality for this disease is 95 percent over five years, which means this is the largest killer of all cancers for both men and women," he noted. "So, anything that would decrease mortality is welcomed. And, because they're working with a naturally-produced hormone, this work shows that we have the capacity to engineer new treatments that manipulate substances generated by the body, which is appealing, because it avoids the use of therapies based on substances not found in the body that are often toxic. So, this is a positive development."
For additional information on lung cancer treatment, visit the American Cancer Society.
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