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.

Related Articles


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 January 30, 2015 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 January 30, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, January 30, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Oxfam Calls for Massive Aid for Ebola-Hit West Africa

Oxfam Calls for Massive Aid for Ebola-Hit West Africa

AFP (Jan. 29, 2015) Oxfam International has called for a multi-million dollar post-Ebola "Marshall Plan", with financial support given by wealthy countries, to help Guinea, Sierra Leone and Liberia to recover. Duration: 01:10 Video provided by AFP
Powered by NewsLook.com
Are We Winning The Fight Against Ebola?

Are We Winning The Fight Against Ebola?

Newsy (Jan. 29, 2015) The World Health Organization announced the fight against Ebola has entered its second phase as the number of cases per week has steadily dropped. Video provided by Newsy
Powered by NewsLook.com
Calif. Health Officials Campaign Against E-Cigarettes

Calif. Health Officials Campaign Against E-Cigarettes

Newsy (Jan. 29, 2015) The California Health Department says e-cigarettes are a public health risk for both smokers and those who inhale e-cig smoke secondhand. Video provided by Newsy
Powered by NewsLook.com
Measles Scare Sends 66 Calif. Students Home

Measles Scare Sends 66 Calif. Students Home

AP (Jan. 29, 2015) Officials say 66 students at a Southern California high school have been told to stay home through the end of next week because they may have been exposed to measles and are not vaccinated. (Jan. 29) 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:

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