Navigation Links
Cancer drugs my build and not tear down blood vessels
Date:11/9/2008

Scientists have thought that one way to foil a tumor from generating blood vessels to feed its growth a process called angiogenesis was by creating drugs aimed at stopping a key vessel growth-promoting protein. But now the opposite seems to be true.

Researchers at the Moores Cancer Center at the University of California, San Diego (UCSD) in La Jolla have found evidence that blocking that protein target, called VEGF, or vascular endothelial growth factor, doesn't really halt the process at all. Instead, cutting levels of VEGF in a tumor actually props up existing blood vessels, making them stronger and more normal, and in some cases the tumors larger. But as a result, the tumor is more vulnerable to the effects of chemotherapy drugs.

In a paper appearing online November 9, 2008 in the journal Nature, David Cheresh, Ph.D., professor and vice chair of pathology at the UC San Diego School of Medicine and the Moores UCSD Cancer Center and his co-workers mimicked the action of anti-angiogenesis drugs by genetically reducing VEGF levels in mouse tumors and inflammatory cells in various cancers, including pancreatic cancer. They also used drugs to inhibit VEGF receptor activity. In every case, blood vessels were made normal again.

The researchers say the findings provide an explanation for recent evidence showing that anti-angiogenesis drugs such as Avastin can be much more effective when combined with chemotherapy. The results may lead to better treatment strategies for a variety of cancers.

"We've discovered that when anti-angiogenesis drugs are used to lower the level of VEGF within a tumor, it's not so much a reduction in the endothelial cells and losing blood vessels as it is an activation of the tumor blood vessels supporting cells," said Cheresh. "This enables vessels to mature, providing a conduit for better drug delivery to the tumor. While the tumors initially get larger, they are significantly more sensitive to chemotherapeutic drugs."

As a result, Cheresh said, the findings may provide a new strategy for treating cancer. "It means that chemotherapy could be timed appropriately. We could first stabilize the blood vessels, and then come in with chemotherapy drugs that are able to treat the cancer."

Co-author Randall Johnson, Ph.D., professor of biology at UCSD, Cheresh and their colleagues showed in a related paper in the same journal that tumors were more susceptible to drugs after inflammatory cells lost the ability to express VEGF.

"These two papers define a new mechanism of action for VEGF and for anti-angiogenesis drugs," Cheresh said. "It appears that the drugs, in shutting down VEGF activity, are actively maturing blood vessels, causing them to become stable and more normal, as opposed to reducing blood vessels."

VEGF normally promotes the growth of endothelial cells, which in turn helps build new blood vessels in tumors. But tumor blood vessels are built poorly and do a terrible job of carrying blood and oxygen and drugs. Cutting VEGF levels in the tumor in turn increases the activity of cells called pericytes that surround the blood vessels, stabilizing them and making them more susceptible to chemotherapy, Cheresh explained.

Cheresh's group found that receptors for VEGF and another growth-promoting protein, PDGF, form a complex that turns off PDGF and the activity of the blood vessel-support cells. Tumors make too much VEGF in their haste to form blood vessels, which turns on the receptor complex. "When you take away the VEGF, you 'take the foot off of the brake,'" he said, allowing the pericytes to go to work, maturing blood vessels. The same mechanism is at work during wound repair.

Cheresh said that the results show that the host response to the cancer whether or not it is making blood vessel-maturing cells, for example is critical in terms of susceptibility to therapy. "It's not just about the therapy, but also what the host does in response to the cancer that makes a difference whether a tumor lives or dies, and if it's susceptible to a drug or not. We can change the host response to the cancer, which is otherwise resistant, and make the vessels more mature, temporarily increasing blood flow to the cancer. We're sensitizing the cancer."

The type of solid tumor should not matter, since the mechanism isn't specific to a particular kind of tumor, he noted. That the quality of the tumor's blood vessels could dictate the patient's response to chemotherapy could be one reason that two patients with similar cancers respond differently to the same therapy.

Cheresh believes that some drug regimens may need to be reexamined. "We have to test available regimens and perhaps restructure the way that we give drugs," he said. "We may be giving the right drugs, but we may not be giving them in the right order. We're just beginning to understand how it works."


'/>"/>

Contact: Steve Benowitz
sbenowitz@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

Related medicine news :

1. Cost of treating colorectal cancer can vary by thousands per patient
2. Barry Manilow Brings Valentines and Music to New York With Concert to Raise Funds for Breast Cancer Research
3. AMA Immediate Past President Ron Davis Loses Battle With Cancer, Leaves Enduring AMA and Public Health Legacy
4. ESF workshop makes major advance in cancer radiotherapy
5. More People Living Longer After Cancer Diagnosis
6. Researchers find predictive tests and early treatment delay progression of blood cell cancer
7. Negative Cancer Messages Backfire With Blacks
8. Lung Cancer Alliance-Georgia Issues Third Annual State-Specific Report Card on Lung Cancer
9. Free Web Site Lists Breast Cancer Clinical Trials
10. Lung Cancer Alliance Releases 4th Annual Report Card on Lung Cancer
11. Migraine Might Lower Breast Cancer Risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/8/2016)... Washington, D.C. (PRWEB) , ... February 08, 2016 ... ... has officially launched its newly redesigned website, federallabs.org . The site houses ... technologies or license available federal technologies through the process called technology transfer (T2). ...
(Date:2/8/2016)... Houma, LA (PRWEB) , ... February 08, 2016 ... ... Louisiana from offices in Houma, LA, celebrates the beginning of a new charity ... raised to assist Court Appointed Special Advocates (CASA). In the belief that children ...
(Date:2/8/2016)... ... February 08, 2016 , ... Brenton Engineering , ... bags, and flow wrapped products at WestPack 2015, February 9-11, in Anaheim, California. ... up to semi-automatic or fully-automatic case packing with a small footprint, rugged, highly ...
(Date:2/8/2016)... ... February 08, 2016 , ... Steve Helwig & Associates Insurance ... new community enrichment program, has teamed up with Citizens Opposed to Domestic Abuse in ... intimate abuse. To support all those victimized by the fear of violence in their ...
(Date:2/8/2016)... ... February 08, 2016 , ... Delta Dental of California and its affiliated ... , Gary D. Radine, who recently retired as president and CEO of Delta Dental ... 2015 CEO of the Year , helped lead the effort to raise funds for ...
Breaking Medicine News(10 mins):
(Date:2/8/2016)... 2016  HemaFlo Therapeutics, Inc. announced today that the United ... Number 9,119,880 covering the use of NephroFlow to treat acute ... HemaFlo,s founder, said, "We are pleased to secure our rights ... Peterson , PhD, HemaFlo,s founder, said, "We are pleased to ... --> Dale Peterson , PhD, HemaFlo,s founder, said, ...
(Date:2/8/2016)... Feb. 8, 2016 Palatin Technologies, Inc. ... receptor-specific peptide therapeutics for the treatment of diseases ... announced today that the United States Patent and ... Allowance for U.S. Patent Application Serial Number 14/313,258 ... methods of treating female sexual dysfunction using the ...
(Date:2/5/2016)... , Feb. 5, 2016 Amgen (NASDAQ: AMGN ... Annual Global Healthcare Conference at 9:15 a.m. ET on Wednesday, ... . David W. Meline , executive vice president and ... Live audio of the presentation can be accessed from the ... A replay of the webcast will also be available on ...
Breaking Medicine Technology: