Title:Microbial Enzymes used in Prodrug Activation for Cancer Therapy: Insights and Future Perspectives
Volume: 22
Issue: 7
Author(s): Rakhi Dhankhar, Anubhuti Kawatra, Aparajita Mohanty and Pooja Gulati*
Affiliation:
- Medical Microbiology and Bioprocess Technology Laboratory, Department of Microbiology, Maharshi Dayanand University, Rohtak, Haryana,India
Keywords:
ADEPT, GDEPT, carboxypeptidase, cytosine deaminase, EPT (enzyme prodrug therapy), nitroreductase, purine
nucleoside phosphorylase.
Abstract: Enzyme prodrug therapy has gained momentum in recent years due to its ability to improve
therapeutic index (benefits versus toxic side-effects) and efficacy of chemotherapy in cancer
treatment. Inactive prodrugs used in this system are converted into active anti-cancerous drugs by
enzymes, specifically within the tumor cells. This therapy involves three components namely prodrug,
enzyme and gene delivery vector. Past reports have clearly indicated that the choice of enzyme
used is the major determinant for the success of this therapy. Generally, enzymes from nonhuman
sources are employed to avoid off-target toxicity. Exogenous enzymes also give better control
to the clinician regarding the calibration of treatment by site-specific initiation. Amongst these
exo-enzymes, microbial enzymes are preferred due to their high productivity, stability and ease of
manipulation. The present review focuses on the commonly used microbial enzymes, particularly
cytosine deaminase, nitroreductase, carboxypeptidase, purine nucleoside phosphorylase in prodrug
activation therapy. Various aspects viz. source of the enzymes, types of cancer targeted, mode of action
and efficacy of the enzyme/prodrug system, efficient vectors used and recent research developments
of each of these enzymes are comprehensively elaborated. Further, the results of the clinical
trials and various strategies to improve their clinical applicability are also discussed.
