Transcription of Strategies for Enzyme/Prodrug Cancer Therapy
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Strategies for Enzyme/Prodrug Cancer Therapy
3314 Vol. 7, 3314 3324, November 2001 Clinical Cancer Research Minireview Strategies for Enzyme/Prodrug Cancer Therapy1. Guang Xu and Howard L. McLeod2 expressed only at low concentrations in normal tissues (11, 12). Washington University School of Medicine, Departments of The protein must achieve sufficient expression in the tumors and Medicine, Molecular Biology & Pharmacology, and Genetics have high catalytic activity (13). The prodrug should be a good and the Siteman Cancer Center, St. Louis, Missouri 63110 substrate for the expressed enzyme in tumors but not be acti- vated by endogenous enzyme in nontumor tissues. It must be able to cross the tumor cell membrane for intracellular activa- Abstract tion, and the cytotoxicity differential between the prodrug and The selective activation of prodrug (s) in tumor tissues its corresponding active drug should be as high as possible. It is by exogenous enzyme(s) for Cancer Therapy can be accom- preferred that the activated drug be highly diffusible or be plished by several ways, including gene-directed enzyme actively taken up by adjacent nonexpressing Cancer cells for a prodrug Therapy (GDEPT), virus-directed enzyme prodrug bystander killing effect, the ability to kill any neighboring Therapy (VDEPT), and antibody-directed enzyme prodrug nonexpressing cells (13).
Minireview Strategies for Enzyme/Prodrug Cancer Therapy1 Guang Xu and Howard L. McLeod2 Washington University School of Medicine, Departments of …
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