Heart Hormones Beat Back Cancers in Mice

THURSDAY Feb. 28, 2008 -- New research offers early evidence that hormones produced by the heart to control both blood pressure and volume could be harnessed to treat -- and possibly cure -- a wide range of cancers.

Following a month of intravenous treatment with any of four human cardiac peptide hormones, mice engineered to develop human pancreatic and breast cancer experienced dramatic results: On average, 54 percent of those with breast cancer and 37 percent of those with pancreatic cancer were cured, without tumor recurrence or treatment side effects.

Even tumor shrinkage among non-cured mice was striking, with size reductions of 90-plus percent. And a more detailed analysis, hormone-by-hormone, revealed even stronger anti-cancer properties among certain hormones. In such best-case scenarios, the most effective hormones provoked full tumor elimination -- without surgery, chemotherapy or any other additional treatment -- in two-thirds of the mice with breast cancer and 80 percent of the mice with pancreatic cancer.

"This raises hope for turning cancer -- even when not fully cured -- into a chronic disease," said study author Dr. David L. Vesely, director of the department of molecular pharmacology and physiology at the University of South Florida's Cardiac Hormone Center, in Tampa.

Vesely is scheduled to present his findings April 9 at the Experimental Biology annual conference in San Diego. The findings were originally published in the journal in vivo last year.

"For 350 years, the heart has been thought of simply as a pump," Vesely said. "But we now know it makes hormones that lower your blood pressure and get rid of salt and water. So, first we took four of them that all come from the same gene, and looked at them in laboratory cell cultures, and found that they essentially eliminated 97 percent of exposed cancer cells within 24 hours."

With funding largely from the U.S. Veteran's Administration, the research team then grew human cancer cells in 1-month-old male and female mice, focusing first on pancreatic cancer, which Vesely described as the "worst of all," given the fast pace of its development, its poor treatment track record, and a mean survival rate of just four months.

Nearly 34,000 Americans are diagnosed with pancreatic cancer each year, and 32,000 die of the disease annually.

Some of the pancreatic cancer mice received a saline solution, while others were exposed to a month-long regimen of one of four cardiac hormones: long acting natriuretic peptide (LANP), vessel dilator (VDL), kaliruretic peptide (KP), or atrial natriuretic peptide (ANP).

ANP was found to provide the best anti-cancer effect, eliminating tumors in four of five treated mice. Among those not fully cured, VDL provided the best cancer reduction -- bringing exposed tumors down to just 2 percent of their largest size.

After a year, the researchers found that all the cured mice remained cancer-free. Based on the fact that the normal life span for a mouse is about one year, Vesely and his colleagues concluded that all the treated mice ended up dying of old age, not cancer.

Vesely, who noted that his wife died of breast cancer about five years ago, then turned his focus to that cancer.

He said that in similar mouse experiments, treatments with VDL and KP hormones both produced a 67 percent tumor elimination rate.

"We never expected results this good, of course," he said. "And I don't want to get too carried away here. But if this works in humans, it would be spectacular. Because, of course, one out of every two families [experiences] cancer."

Human trials -- funded by the private San Diego-based firm Kalos Therapeutics -- are to begin within 12 to 18 months. If all goes well, Vesely predicted that a hormone treatment could become available within three years.

However, Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, cautioned that while the notion of a heart hormone cancer treatment has a "seductive" appeal, much more research is required.

"Unfortunately, in general, we see a lot of experiments that seem promising in test tubes and animals but for whatever reason don't translate into anything that has treatment benefit," he said. "And specifically, in this case, we're talking about normal hormones already in circulation in our body, and normal receptors on cancer cells.

"So, in a perhaps simplistic, but nonetheless important, way, the question then arises: Why do people get cancer in the first place if this hormonal mechanism is so effective?" Lichtenfeld said. "And I do not see that the researchers clearly suggest an underlying rational mechanism to explain why this would happen and work in humans.

"So, I understand here that a researcher has lost a wife and a mother to cancer, and I know it's personal," he acknowledged. "And I've certainly learned to never say never. But it would take considerably more replication of this work before I could say this theory will gain traction."

More information

For additional information on current cancer treatment options, visit the American Cancer Society.

Posted: February 2008


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