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PLoS Comput Biol. 2020 Feb 3;16(2):e1007604. doi: 10.1371/journal.pcbi.1007604. eCollection 2020 Feb.

SynToxProfiler: An interactive analysis of drug combination synergy, toxicity and efficacy.

Author information

1
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
2
Helsinki Institute for Information Technology (HIIT), Aalto University, Espoo, Finland.
3
Department of Mathematics and Statistics, University of Turku, Quantum, Turku, Finland.

Abstract

Drug combinations are becoming a standard treatment of many complex diseases due to their capability to overcome resistance to monotherapy. In the current preclinical drug combination screening, the top combinations for further study are often selected based on synergy alone, without considering the combination efficacy and toxicity effects, even though these are critical determinants for the clinical success of a therapy. To promote the prioritization of drug combinations based on integrated analysis of synergy, efficacy and toxicity profiles, we implemented a web-based open-source tool, SynToxProfiler (Synergy-Toxicity-Profiler). When applied to 20 anti-cancer drug combinations tested both in healthy control and T-cell prolymphocytic leukemia (T-PLL) patient cells, as well as to 77 anti-viral drug pairs tested in Huh7 liver cell line with and without Ebola virus infection, SynToxProfiler prioritized as top hits those synergistic drug pairs that showed higher selective efficacy (difference between efficacy and toxicity), which offers an improved likelihood for clinical success.

PMID:
32012154
DOI:
10.1371/journal.pcbi.1007604
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Conflict of interest statement

The authors have declared that no competing interests exist.

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