Antimetabolites interfere with DNA and RNA synthesis by acting as false metabolites, which are incorporated into the DNA strand or block essential enzymes, so that DNA synthesis is prevented.13 Most agents are cell cycle phase specific for S phase. These agents are most effective when used against rapidly cycling cell populations and are consequently more effective against fast-growing tumours than slow-growing tumours. Major toxicities occur in the haematopoietic and gastrointestinal systems. Examples include Methotrexate, 5-Fluorourocil and Cytosine Arabinoside.1, 7, 11
Hypomethylating agents represent a class of drugs that may restore normal gene function to genes responsible for cell division and differentiation.14 Hypomethylating agents may function as biological response modifiers by affecting cytokine cell signaling.12 These agents may be identified as antimetabolites and they include 5-azacytidine and Decitabine.
Learning activity
Choose an antimetabolite and a hypomethylating agent and discuss its:
- Indications in cancer control.
- Mechanism of action.
- Adverse effects.
- Administration considerations.