Left: Dose-based synergy results from a decrease in dose to achieve the same effect, quantified with the CI value.
Right: Effect-based synergy results from an increase in the maximum effect, quantified by Bliss scoring.

Drug Combination Methods: Dose-based and Effect-based now Merged into One Approach

Oss, April, 9th, 2020 – Much research has gone into defining the best way of determining compound synergies in an in vitro assay. From this, two basic methods have evolved, the curve shift analysis and the combination matrix experiment with Bliss-scoring. The curve shift analysis determines synergy as a decrease in dose to achieve the same effect (Dose-based), which is quantified with the CI value. The Bliss approach bases synergy on an increase in the maximum effect (Effect-based). The synergistic mechanism of a specific combination may result in either one or the other, or both. NTRC has now merged the two methods into one approach, generating a comprehensive view on synergistic effects.

An advantage of NTRC’s approach is the use of full dose response curves. This takes the sigmoidal nature of drug-effect relations into account, as illustrated on the right (Chou, 2006). The exponential behaviour may be overlooked in a dose-matrix approach, which may lead to a misinterpretation of the combination effects.

In case a synergy is found in a SynergyFinder™ study, an experimental replicate will be performed as part of the workplan. The reproducibility of NTRC’s cancer cell line profiling methods is very high (Uitdehaag et al., 2015; Uitdehaag et al., 2016). NTRC also offers SynergyScreen™, in which one compound is profiled against a large library of reference anti-cancer agents.

NTRC is a precision medicine company dedicated to discovering new anti cancer drug candidates. It is our mission to help you finding a mechanistic hypothesis before entering the clinic. We provide cell-based profiling services, target residence time measurements and biochemical profiling. We can study a wide range of cancer cells, primary patient material and immune cells in vitro, in isolation and in coculture, after exposure to monotherapy and combination therapy. Keywords are: Quality. Flexibility. Short Turnaround Time.