2015 Antineoplastics

L-ASPARAGINASE

Mechanism

  • in normal cells, the asparagine used for protein synthesis is generated from aspartate by asparagine synthase; asparagine outside the cell is converted to aspartate by L-ASPARAGINASE before being pumped into the cell and converted back to asparagine

  • administration of L-ASPARAGINASE causes selective toxicity because some tumour cells lack asparagine synthase (i.e., they require an exogenous sources of L-asparagine for protein synthesis), therefore decreasing the asparagine concentration by giving L-ASPARAGINASE deprives tumour cells of asparagine

  • used to treat childhood acute lymphocytic leukemia

  • main side effects are hypersensitivity reactions (fever, chills, nausea/vomiting, skin rash and urticaria) because L-ASPARAGINASE is isolated from bacteria

  • usually used with other agents; sequence of drug administration is critical, for example:
    • if METHOTREXATE is given first, you have synergistic cytotoxicity ( due to synchrony)
    • if L-ASPARAGINASE is given first, the METHOTREXATE cytotoxicity is reduced as METHOTREXATE cell kill is dependent upon synthesis of the enzymes necessary for DNA synthesis (DHFR and thymidylate synthase, specifically)
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 11-apr-15 9:39 AM