26-03-2018

NTRC expands SynergyFinder™ platform with triple combination testing

Many cancer therapies consist of mixtures in which multiple molecular entities work together to halt cancer growth, or to overcome emerging resistance mechanisms. In some cases, as much as five compounds are be combined. Development of such therapy is hampered by the vast number of possible combinations and it is imperative to select candidates in high throughput in vitro experiments, and only to progress the most promising mixtures for further in vivo testing.

NTRC’s SynergyFinder™ platform allows parallel in vitro screening of combinations and distinguishes additive from synergistic effects [1]. In the past we showed its excellent performance in discovering novel dual combinations [1]. To contribute to the development of cancer therapy that comprises multiple molecular ingredients, NTRC has expanded its SynergyFinder™ platform. In the new setup, mixtures of three can be tested and the individual contribution of each ingredient to the total synergy can be determined. In one such experiment, NTRC has shown that the FDA-approved combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib can be further supplemented with the PI3K inhibitor pictilisib to enhance synergy (Figure 1). By establishing such super-synergistic combinations in vitro, it is possible to effectively focus resources for in vivo studies on the most successful multi-combinations.

Figure 1: Example of a triple synergistic combination (grey). Red, yellow and blue indicate dabrafenib, trametinib and pictilisib as single agents, respectively.

Literature reference
[1] Uitdehaag et al. (2015) PLoS ONE 10(5), e0125021

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