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Formal Discussion: Some Enzymatic Considerations in Combination Chemotherapy

Yale University School of Medicine, New Haven, Connecticut

A specific example of the effect of two inhibitors acting on a monolinear enzyme sequence in pyrimidine biosynthesis de novo has indicated a lack of even an additive effect of this combination. From this, a more general analysis of enzyme kinetics has indicated the difficulty in obtaining potentiation of action at the enzyme level between 2 agents acting in a particular area of metabolism. Some examples are given for those circumstances in which 2 inhibitors do produce a potentiative effect on the growth of microorganisms or tumors for which there are possible biochemical explanations.

¹ Career Professor of Pharmacology, American Cancer Society.