Biochemical modulation of Anticancer agents

Biochemical modulation of Anticancer agents - A. Valeriote

Biochemical Modulation at the present time defines an area of study in which the intracellular metabolism of a given anti- cancer agent is modulated (usually by a noncytotoxic agent or a cytotoxic agent at sufficiently low dosage to make it non- cytotoxic) in order to either increase the effectiveness of the particular agent against tumor cells or decrease its cytotox- icity against normal cells. The major focus of modulation has been the agents 5-fluorouracil (FUra), arabinofuranosylcytosine (ara-C), methotrexate (MTX) and a few alkylating agents. The major thrust of the studies has been to increase the flow of the anticancer agent along the pathway responsible for the formation of the cytotoxic species: for example, FUra to FUTP or ara-C to ara-CTP. While in most cases the application of research re- sults to clinical trials does not require the subsequent exper- tise of the laboratory researchers, application of biochemical modulatory schemes to clinical protocols necessitate a dramatic break with the past procedures.