Drug combination studies and their synergy quantification using the Chou-Talalay method

TC Chou - Cancer research, 2010 - AACR
Cancer research, 2010AACR
This brief perspective article focuses on the most common errors and pitfalls, as well as the
do's and don'ts in drug combination studies, in terms of experimental design, data
acquisition, data interpretation, and computerized simulation. The Chou-Talalay method for
drug combination is based on the median-effect equation, derived from the mass-action law
principle, which is the unified theory that provides the common link between single entity
and multiple entities, and first order and higher order dynamics. This general equation …
Abstract
This brief perspective article focuses on the most common errors and pitfalls, as well as the do's and don'ts in drug combination studies, in terms of experimental design, data acquisition, data interpretation, and computerized simulation. The Chou-Talalay method for drug combination is based on the median-effect equation, derived from the mass-action law principle, which is the unified theory that provides the common link between single entity and multiple entities, and first order and higher order dynamics. This general equation encompasses the Michaelis-Menten, Hill, Henderson-Hasselbalch, and Scatchard equations in biochemistry and biophysics. The resulting combination index (CI) theorem of Chou-Talalay offers quantitative definition for additive effect (CI = 1), synergism (CI < 1), and antagonism (CI > 1) in drug combinations. This theory also provides algorithms for automated computer simulation for synergism and/or antagonism at any effect and dose level, as shown in the CI plot and isobologram, respectively. Cancer Res; 70(2); 440–6
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