There’s a promising anticancer drug on the scene, but it has what scientists thought was a serious shortcoming: It breaks down quickly in water or blood. That makes it hard to deliver the right dose to patients.
But here’s a surprise. City of Hope scientists found that the main breakdown product might be a better drug to begin with.
Katarzyna Lamparska, left, and Steven Smith (Photo by Darrin S. Joy)
The U.S. Food and Drug administration approved decitabine as a treatment for certain bone marrow diseases. Researchers are studying decitabine and closely related drugs for use against cancers, as well.
These drugs belong to a class called epigenetic drugs. They work by upsetting the structure of cancer cells’ chromosomes. This disruption can be lethal to cancer cells. Decitabine also makes it easier for standard chemotherapy to damage DNA and kill cancer cells.
But decitabine is unstable. So researchers led by Staff Scientist Katarzyna Lamparska, Ph.D., and Professor Steven Smith, Ph.D., both of the Division of Urology and Urologic Oncology and Beckman Research Institute, took a closer look at the drug.
The surprise result
The team knew that, in the body, decitabine breaks down mostly into a compound called GuaUre-dR. That’s short for 2’-deoxyriboguanylurea. Team members suspected GuaUre-dR plays a role in the anticancer effects of decitabine.
Working with cells in the lab, the scientists studied how GuaUre-dR interacts with DNA. They found that GuaUre-dR actually causes many of the changes to DNA that scientists believed were caused by decitabine.
Even better, GuaUre-dR is stable.
Smith believes that giving patients GuaUre-dR instead of decitabine could help physicians better control their dosing. The researchers hope that GuaUre-dR may be developed as an anticancer drug.
Researchers on the study also included Jarrod Clark, Gail Babilonia, Victoria Bedell and Wesley Yip. The study was published online July 31 in Nucleic Acids Research.
NIH grants: CA10252, CA136055 and CA033572-27