Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.1 (cytosine deaminase)
 747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several recent reports have demonstrated that anticancer drugs can be generated site-selectively at solid tumors by monoclonal antibody-enzyme conjugates targeted to antigens on tumor cell surfaces. The first step in this drug targeting approach involves the delivery of the enzyme conjugate to a tumor cell population. After the conjugate has localized within the tumor and cleared from non-target tissues, a relatively non-cytotoxic drug precursor (prodrug) is administered. Upon contact with the targeted enzyme, the prodrug is converted into a toxic drug. Several examples are presented to illustrate this targeting strategy. Monoclonal antibody-beta-lactamase conjugates have been developed to activate a panel of anticancer prodrugs that are mechanistically dissimilar. The antitumor activities of the monoclonal antibody-beta-lactamase conjugate/prodrug combinations exceed those obtained by systemic drug administration, and are immunologically specific. In another example involving targeted cytosine deaminase for the generation of 5-fluorouracil, it is shown that as much as 17 times more drug can be delivered within a tumor compared to when 5-fluorouracil is administered alone. The method of using targeted enzymes for prodrug activation can be extended to include prodrugs that release very potent drugs, such as palytoxin, a marine natural product, and to treat cells that have the multidrug resistance phenotype. Some of the requirements for successful therapy with this approach for cancer therapy are discussed.
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PMID:Selective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates. 788 77