Why Certain Cancer Treatments Cause High Blood Pressure

Aug 04, 2009

(PhysOrg.com) -- Drugs that block the formation of new blood vessels that feed tumor growth are helping some cancer patients enjoy longer lives.

But they come with a price: Studies show that up to a third of all patients who take the anti-angiogenesis drugs develop high . Scientists at Duke University Medical Center may have figured out why.

"Anti-angiogenesis drugs like Avastin, Sutent, or Nexavar inhibit an important substance called vascular endothelial growth factor (VEGF) that stimulates the creation of new vessels that support malignant growth," says Thomas Coffman, MD, a professor of medicine, cell biology and immunology at Duke and the senior author of the study appearing online in the .

"Our studies in mice show that blocking VEGF causes hypertension because it disrupts an important biological system -- the pathway that regulates blood vessel health."

Scientists discovered the connection through experiments in mice. Carie Facemire, PhD, a researcher in Coffman's lab, used an antibody to block a key VEGF receptor called VEGFR2 in the animals.

She found that after about a week, all of the mice that received the antibody experienced a "rapid and sustained" increase in blood pressure. Animals that got a maintained normal blood pressure.

Researchers found that dose mattered. A modest amount of the VEGFR2 antibody didn't do anything to cause a jump in blood pressure, but a high dose equivalent to a therapeutic amount a patient would receive, did cause blood pressure to rise.

"The higher doses of anti-angiogenesis drugs that patients need to keep their cancers from growing translate into a significant increase in risk for hypertension and, by extension, for cardiovascular complications," says Coffman.

To further determine what role nitric oxide dysregulation plays in promoting hypertension, Coffman gave the mice in the placebo group a compound to block nitric oxide production. Sure enough, those mice developed high blood pressure, too, just like the group that got the VEGFR2 antibody.

Coffman says as cancer patients live longer, side effects like hypertension, which might once have seemed less important, take on new meaning. "Long-term hypertension can have serious consequences," he says.

Herbert Hurwitz, MD, a medical oncologist at Duke and one of the first to document how Avastin and other anti-angiogenesis drugs provide benefit to cancer patients, says for most patients, anti-angiogenesis drugs are helpful and any resulting hypertension is usually manageable with traditional blood pressure medications.

"However, these new findings are important since they point to specific ways to better protect against the risks of long-term hypertension. They also suggest ways to protect patients against other serious but uncommon side effects, like stroke or heart attack."

The study was funded by the National Institutes of Health, the Mandel Center for and Atherosclerosis, and the Research Service of the Department of Veteran's Affairs.

Carie Facemire is the lead author on the study. Additional Duke researchers who contributed to it include Andrew Nixon, Robert Griffiths and Herbert Hurwitz.

Provided by Duke University (news : web)

Explore further: Novartis Japan hit with suspension over side-effect reporting

add to favorites email to friend print save as pdf

Related Stories

Vessel-thwarting antibody might help starve cancerous tumors

Nov 01, 2007

An antibody might offer a safe and effective complement to anti-cancer therapies designed to starve malignant tumors by pruning the blood vessels that feed them, researchers report in the November 2 issue of the journal Cell.

Another way to grow blood vessels

Feb 21, 2008

Researchers at Dana-Farber Cancer Institute have found a previously unknown molecular pathway in mice that spurs the growth of new blood vessels when body parts are jeopardized by poor circulation.

Reducing side-effects of painkillers

Sep 12, 2006

Cardiff University researchers have increased the understanding of why some painkillers increase the risk of heart attack and stroke.

Recommended for you

Use new meningitis vaccines only for outbreaks

15 hours ago

(AP)—A U.S. panel on Thursday recommended that two new meningitis vaccines only be used for rare outbreaks, resisting tearful pleas to give it routinely to teens and college students.

New antibiotic avycaz approved

19 hours ago

(HealthDay)—The combination antibiotic Avycaz (ceftazidime-avibactam) has been approved by the U.S. Food and Drug Administration to treat adults with complicated infections of the intra-abdominal area or urinary tract, ...

Tagging drugs to fight counterfeit medicines

Feb 25, 2015

The U.S. and other countries are enacting rules to clamp down on the sales of fake pharmaceuticals, which pose a public health threat. But figuring out a system to track and authenticate legitimate drugs still faces significant ...

Watchdog group seeks FDA ban of antifungal tablets

Feb 24, 2015

(AP)—A consumer safety group is calling on the Food and Drug Administration to pull certain antifungal tablets off the market, saying there are safer medicines that do not carry risks of liver damage.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Aug 04, 2009
Angeogenisis is a survival action to reduce thermal rise and accelerated mitosis in malfunctioning cells and cell groups. To reduce this by ANY means is ill-advised! COOL the cell, or cells malfunctioning, and the process will stop!

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.