Featured Research

from universities, journals, and other organizations

Prodrug Could Help Curb Skin Toxicity Related To EGFR-inhibiting Cancer Drugs

Date:
September 3, 2009
Source:
Thomas Jefferson University
Summary:
There may be a way around the harsh skin toxicity associated with a widely used cancer drug, according to a new study.

There may be a way around the harsh skin toxicity associated with a widely used cancer drug, according to a study published online this week in Cancer Biology and Therapy by researchers from City of Hope and the Kimmel Cancer at Jefferson.

Cetuximab (Erbitux) is a monoclonal antibody that binds to and inhibits the epidermal growth factor receptor (EGFR). It is widely used to treat colorectal cancer and head and neck cancer. Although cetuximab and other EGFR inhibitors are associated with a lower rate of side effects compared with conventional chemotherapy, adverse effects of the drugs often include a dose-limiting skin rash and gastrointestinal symptoms.

Adverse events in antibody therapy are frequently due to the binding of antibodies to normal tissue in addition to tumor tissue, according to Ulrich Rodeck, M.D., Ph.D., professor of Dermatology and Cutaneous Biology at Jefferson Medical College of Thomas Jefferson University. By "masking" the antibodies so they preferentially bind to the tumor tissue, the toxicity may be reduced or avoided.

"We've designed a prodrug in which the antibody is masked by an engineered form of the antigen, preventing it from binding to antigen on normal tissue," Dr. Rodeck said. "However, when the antibody reaches the tumor tissue, enzymes prevalent at tumor sites cleave the mask off, and the antibody can now engage the antigen at the tumor site."

The prodrug contains the antigen binding sites of two different EGFR-specific antibodies: 425 (matuzumab) and C225 (cetuximab). Each antibody is connected via peptide linker to the antigen recognized by the opposite antibody. The linkers contain sites susceptible to proteolytic cleavage by metalloprotease 9 (MMP-9), an enzyme that is frequently overexpressed in epithelial malignancies. Cleavage of the complex leads the antibodies to become "unmasked" and able to bind to the antigens on the tumor cells.

"This work provides proof-of-principle evidence that the concept is feasible, and sets the stage for future studies using tumors grown in vivo," Dr. Rodeck said.

This study was led by Dr. Rodeck and John C. Williams, Ph.D., assistant professor of molecular medicine and director of the x-ray crystallography program at City of Hope. The first author is Joshua Donaldson, a graduate student at Jefferson. The print version of the study will be published in the November 15 issue of Cancer Biology and Therapy.


Story Source:

The above story is based on materials provided by Thomas Jefferson University. Note: Materials may be edited for content and length.


Cite This Page:

Thomas Jefferson University. "Prodrug Could Help Curb Skin Toxicity Related To EGFR-inhibiting Cancer Drugs." ScienceDaily. ScienceDaily, 3 September 2009. <www.sciencedaily.com/releases/2009/09/090901122635.htm>.
Thomas Jefferson University. (2009, September 3). Prodrug Could Help Curb Skin Toxicity Related To EGFR-inhibiting Cancer Drugs. ScienceDaily. Retrieved April 25, 2014 from www.sciencedaily.com/releases/2009/09/090901122635.htm
Thomas Jefferson University. "Prodrug Could Help Curb Skin Toxicity Related To EGFR-inhibiting Cancer Drugs." ScienceDaily. www.sciencedaily.com/releases/2009/09/090901122635.htm (accessed April 25, 2014).

Share This



More Health & Medicine News

Friday, April 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Fungus Killing Bats, Spreading in US

Deadly Fungus Killing Bats, Spreading in US

AP (Apr. 24, 2014) A disease that has killed more than six million cave-dwelling bats in the United States is on the move and wildlife biologists are worried. White Nose Syndrome, discovered in New York in 2006, has now spread to 25 states. (April 24) Video provided by AP
Powered by NewsLook.com
Companies Ramp Up Wellness to Lower Health Costs

Companies Ramp Up Wellness to Lower Health Costs

AP (Apr. 24, 2014) That little voice telling you to exercise, get in shape and get healthy is probably coming from your boss. More companies are beefing up wellness programs to try and cut down their health care costs. (April 24) Video provided by AP
Powered by NewsLook.com
Blood From World's Oldest Woman Suggests Life Limit

Blood From World's Oldest Woman Suggests Life Limit

Newsy (Apr. 24, 2014) Scientists say for the extremely elderly, their stem cells might reach a state of exhaustion. This could limit one's life span. Video provided by Newsy
Powered by NewsLook.com
FDA Wants To Ban Sales Of E-Cigarettes To Minors

FDA Wants To Ban Sales Of E-Cigarettes To Minors

Newsy (Apr. 24, 2014) The Food and Drug Administration wants to crack down on the use of e-cigarettes, banning the sale of the product to minors. Video provided by Newsy
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