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 October 23, 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 October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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