Advertisement

Thalidomide benefits, dangers caused by similar mechanism

Understanding how the drug causes birth defects and also kills cancer could lead to new drugs with similar anti-cancer effects, researchers say.

By Stephen Feller
In a tumor cell, thalidomide makes a particular protein complex, highlighted in yellow, disappear. This is the same mechanism causes serious malformations in unborn children, but a new understanding of it could lead to the creation of safer drugs with the same effect. Photo by Florian Bassermann/Technical University of Munich
In a tumor cell, thalidomide makes a particular protein complex, highlighted in yellow, disappear. This is the same mechanism causes serious malformations in unborn children, but a new understanding of it could lead to the creation of safer drugs with the same effect. Photo by Florian Bassermann/Technical University of Munich

MUNICH, Germany, June 17 (UPI) -- The drug thalidomide was used briefly in the 1950s and 1960s as a sedative for pregnant women until it was found to cause serious birth defects and was pulled from the market.

German researchers have found in a recent study, however, that the mechanism in thalidomide causing the birth defects is similar to the anti-cancer effects of two derivatives of the drug because of its effect on the immune system.

Advertisement

The German company Grunenthal Group issued an apology in 2012 for the effects of thalidomide, which was prescribed for morning sickness in pregnant women more than 50 years ago, after it was found to be the cause of birth defects.

It was later found that the drug had beneficial uses, including healing mouth sores in AIDS patients in 1997 and a potential role against pancreatic cancer in 2005.

The cancer finding led to the design of derivative drugs, lenalidomide and pomalidomide, immunomodulatory drugs used to inhibit certain cancers, such as bone marrow cancers like multiple myeloma. While the derivatives also pose risk for birth defects -- they are not given to pregnant women who have cancer -- the drugs have become useful tools against the disease.

Advertisement

Previous research established that the cellular protein cereblon plays a significant role in the function of immunomodulatory drugs, binding to the proteins CD147 and MCT1. By prevening proteins from binding with cereblon, the two proteins cannot be activated.

For the new study, published in the journal Nature Medicine, the researchers looked to find the specific effects of preventing this protein interaction, finding it prevents the formation of new blood vessels -- an explanation for both improper growth of a fetus and disruption in the growth of a tumor.

"The mechanisms are identical," Dr. Florian Bassermann, a researcher in the department of internal medicine at the Technical University of Munich's University Hospital, said in a press release. "A specific inactivation of the protein complex resulted in the same developmental defects observed after thalidomide treatment."

The results of the study may help in two areas, the researchers say, in developing a test to find the efficacy of thalidomide or derivatives of it against individual patients' cancer, and the potential development of other drugs aiming to block the CD147 and MCT1 proteins to similarly prevent the formation of blood vessels and starve tumors to death.

Latest Headlines