Toward Reducing The Toxic Side Effects of Cancer Chemotherapy
An advance that may speed the use of "prodrug chemotherapy" - one of the most promising new strategies for reducing the side effects of anti-cancer drugs - is being reported by scientists from Johns Hopkins University's In Vivo Cellular and Molecular Imaging Center (ICMIC).
This two-part chemotherapy involves giving patients the inactive form of an anti-cancer drug (the "prodrug") and an enzyme that changes the prodrug into an active, cancer fighting form. Patients first get the enzyme, which is gradually eliminated from normal tissue but builds up and remains in the tumor. Then patients get the prodrug, which changes into its active and toxic form only upon encountering the enzyme in the tumor.
"Determining the optimal time-window for prodrug injection is therefore of utmost importance for success of these strategies," Zaver M. Bhujwalla, lead author Cong Li and their colleagues note in a report scheduled for the Nov. 29 issue of the weekly Journal of the American Chemical Society. If the prodrug were injected before all the enzyme cleared from normal tissue, it could damage normal tissue and cause body-wide side effects, they say.
The report describes the synthesis and early laboratory testing of the first prodrug-activating enzyme that can be imaged in tissue to time administration of the prodrug. The enzyme produces the active form of the common anti-cancer drug 5-fluorouracil. Its elimination from normal tissue can be monitored with magnetic resonance imaging (MRI) or optical imaging, according to the researchers.