Featured Research

from universities, journals, and other organizations

Combining two peptide inhibitors might block tumor growth

Date:
March 15, 2011
Source:
Ohio State University Medical Center
Summary:
A new study suggests that combining two experimental anticancer peptide agents might simultaneously block formation of new tumor blood vessels while also inhibiting the growth of tumor cells. The findings suggest that the double hit can stifle tumor progression, avoid drug resistance and cause few side effects, say the researchers who developed the agents and evaluated their effectiveness in laboratory and animal tests.

A new study suggests that combining two experimental anticancer peptide agents might simultaneously block formation of new tumor blood vessels while also inhibiting the growth of tumor cells.

This early test of the two agents in a breast cancer model suggests that the double hit can stifle tumor progression, avoid drug resistance and cause few side effects, say researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) who developed the agents and evaluated their effectiveness in laboratory and animal tests.

The scientists designed one of the agents to prevent human epithelial growth factor from interacting with HER-2, a molecule that marks a particularly aggressive form of breast cancer. The other inhibitor blocks the action of vascular endothelial growth factor (VEGF), which stimulates the growth of new blood vessels that tumors need to grow beyond a certain size.

The findings are described in two papers published online in the Journal of Biological Chemistry. One presents the development of a novel VEGF inhibitor; the other describes the HER-2 inhibitor and the preclinical testing of the two agents together.

"When we combined our peptide HER-2 inhibitor with the VEGF peptide that inhibits angiogenesis, we observed significant additive benefits in reducing tumor burdens in preclinical studies," says principal investigator Pravin Kaumaya, professor of obstetrics and gynecology, of molecular and cellular biochemistry, and of microbiology, and director of the division of vaccine development at the OSUCCC -- James.

The strategy of targeting both HER-2 and VEGF pathways should also discourage the development of drug resistance, Kaumaya says, because it simultaneously inhibits two pathways that are essential for tumor survival. "Combined peptide inhibitors might be appropriate in several types of cancer to overcome acquired resistance and provide clinical benefit," he adds.

Peptide inhibitors consist of short chains of amino acids (the VEGF inhibitor is 22 amino acids long) that conform in shape to the active site of the target receptor. In addition, Kaumaya engineered the VEGF peptide to be resistant to protease, an enzyme, thereby increasing its efficacy. The shape of the peptide HER-2 inhibitor engineered by Kaumaya and his colleagues, for example, is highly specific for the HER-2 receptor. It physically binds to the receptor, which prevents another substance, called epithelial growth factor, from contacting the receptor and stimulating the cancer cells to grow.

Other categories of targeted drugs in clinical use are humanized monoclonal antibodies and small-molecule TKI inhibitors. Both groups are associated with severe side effects and are very expensive, Kaumaya says. "We believe peptide inhibitors offer non-toxic, less-expensive alternatives to humanized monoclonal antibodies and small-molecule inhibitors for the treatment of solid tumors, with the potential for improved efficacy and better clinical outcomes," he says.

Funding from NIH supported this research.

Other Ohio State researchers involved in the two studies were Kevin C. Foy, Daniele Vicari, Eric Liotta, Zhenzhen Liu, Gary Phillips and Megan Miller.


Story Source:

The above story is based on materials provided by Ohio State University Medical Center. Note: Materials may be edited for content and length.


Journal References:

  1. Vicari D, Foy KC, Liotta EM, Kaumaya PT. Engineered conformation-dependent VEGF peptide mimics are effective in inhibiting VEGF signaling pathways.. J Biol Chem., Feb 14, 2011 [link]
  2. Foy KC, Liu Z, Phillips G, Miller M, Kaumaya PT. Combination treatment with HER-2 and VEGF peptide mimics induces potent anti-tumor and anti-angiogenic responses in vitro and in vivo. J Biol Chem., Feb 16, 2011 [link]

Cite This Page:

Ohio State University Medical Center. "Combining two peptide inhibitors might block tumor growth." ScienceDaily. ScienceDaily, 15 March 2011. <www.sciencedaily.com/releases/2011/03/110314172324.htm>.
Ohio State University Medical Center. (2011, March 15). Combining two peptide inhibitors might block tumor growth. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2011/03/110314172324.htm
Ohio State University Medical Center. "Combining two peptide inhibitors might block tumor growth." ScienceDaily. www.sciencedaily.com/releases/2011/03/110314172324.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins