A1 Refereed original research article in a scientific journal
SynToxProfiler: An interactive analysis of drug combination synergy, toxicity and efficacy
Authors: Ianevski A, Timonen S, Kononov A, Aittokallio T, Giri AK
Publication year: 2020
Journal: PLoS Computational Biology
Journal name in source: PLoS computational biology
Journal acronym: PLoS Comput Biol
Volume: 16
Issue: 2
Number of pages: 13
ISSN: 1553-734X
eISSN: 1553-7358
DOI: https://doi.org/10.1371/journal.pcbi.1007604
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/46302340
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.
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.
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