Featured Research

from universities, journals, and other organizations

Novel monoclonal antibody offers potential treatment for tumors resistant to VEGF therapy

Date:
December 2, 2011
Source:
American Association for Cancer Research
Summary:
Despite the widespread use of current antiangiogenic cancer therapies, many tumors escape this blockade, which is designed to shut down growth of new blood vessels that feed tumors and spread cancer cells. Now, a study suggests that targeting a novel antiangiogenic receptor may help patients whose cancer does not respond to existing agents.

Despite the widespread use of current antiangiogenic cancer therapies, many tumors escape this blockade, which is designed to shut down growth of new blood vessels that feed tumors and spread cancer cells. Now, a study reported at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics suggests that targeting a novel antiangiogenic receptor may help patients whose cancer does not respond to existing agents.

The experimental agent, PF-03446962, targets activin receptor-like kinase 1 (ALK-1), which is part of the transforming growth factor ß (TGFß) superfamily of receptors that potentially regulate cell growth and differentiation. Known as a tumor suppressor, TGFß can conversely promote invasion and metastasis during the later stages of cancer progression, said Filippo de Braud, M.D., who was director of new drugs at the European Institute of Oncology when the study was conducted and is now chief of the Medical Oncology Department at the National Tumor Institute in Milan, Italy.

Tumor cells frequently lose the growth inhibitory response to TGFß, which makes it a prime target for cancer treatment, he said. PF-03446962, a fully humanized monoclonal antibody, specifically inhibits the activity of ALK-1, which the researchers said is in part regulated by vascular endothelial growth factor (VEGF), the protein that activates angiogenesis and other proangiogenic factors. Shutting down ALK-1 inhibits the VEGF pathway in a manner different from other antiangiogenic treatments now on the market, de Braud said.

Researchers tested PF-03446962 in a phase 1 clinical trial, which demonstrated that the agent exerted anticancer activity in tumors already resistant to VEGF treatment.

De Braud and his colleagues tested eight different doses of PF-03446962 in 44 patients with solid tumors. Results showed a partial response in three patients and stable disease lasting at least four months in seven patients. Most of the patients who benefitted had previously been treated with prior antiangiogenic therapy for lung, renal or liver cancer. Some of these patients did not achieve remission with previous antiangiogenic therapy, "suggesting that ALK-1 can operate as an escape mechanism to VEGF," de Braud said.

The two patients with the longest response (stable disease for about a year) had been diagnosed with adrenocortical cancer and mesothelioma.

The researchers noted that three patients developed telangiectasia, which is dilation of blood vessels near the skin. This disorder is known to be caused by a mutation in the ALK-1 gene, and development of this mild side effect in these patients demonstrates PF-03446962 is affecting ALK-1 function.

"Based on this clinical activity, anti-ALK-1 may be a promising novel strategy to help patients who have failed previous VEGF therapy," de Braud said. The agent might be used on its own or in combination with current antiangiogenic therapy to strengthen inhibition of the VEGF pathway.

Toxicities seen in the phase 1 trial were manageable, a finding that demonstrates that the agent is safe to use, he said.


Story Source:

The above story is based on materials provided by American Association for Cancer Research. Note: Materials may be edited for content and length.


Cite This Page:

American Association for Cancer Research. "Novel monoclonal antibody offers potential treatment for tumors resistant to VEGF therapy." ScienceDaily. ScienceDaily, 2 December 2011. <www.sciencedaily.com/releases/2011/11/111113190532.htm>.
American Association for Cancer Research. (2011, December 2). Novel monoclonal antibody offers potential treatment for tumors resistant to VEGF therapy. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2011/11/111113190532.htm
American Association for Cancer Research. "Novel monoclonal antibody offers potential treatment for tumors resistant to VEGF therapy." ScienceDaily. www.sciencedaily.com/releases/2011/11/111113190532.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) — The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) — Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
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