Abstract
Synergistic drug combinations are commonly sought to overcome monotherapy resistance in cancer treatment. To identify such combinations, high-throughput cancer cell line combination screens are performed; and synergy is quantified using competing models based on fundamentally different assumptions. Here, we compare the behaviour of four synergy models, namely Loewe additivity, Bliss independence, highest single agent and zero interaction potency, using the Merck oncology combination screen. We evaluate agreements and disagreements between the models and investigate putative artefacts of each model's assumptions. Despite at least moderate concordance between scores (Pearson's r >0.32, Spearman's ρ > 0.34), multiple instances of strong disagreement were observed. Those disagreements are driven by, among others, large differences in tested concentrations, maximum response values and median effective concentrations.
Original language | English |
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Pages (from-to) | 2286-2298 |
Number of pages | 13 |
Journal | Drug Discovery Today |
Volume | 24 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2019 |
Externally published | Yes |
Funding
We thank our colleague Dr F. Richards for his constructive feedback and helpful comments on this work. This work was supported by the Leiden International Study Fund, the Netherlands (grant number L17077) to A.H.C.; and the Jo Kolk study fund, the Netherlands to A.H.C.; and the Erasmus + Traineeship fund to A.H.C.; and the KNMP stipend, the Netherlands to A.H.C. We thank our colleague Dr F. Richards for his constructive feedback and helpful comments on this work. This work was supported by the Leiden International Study Fund , the Netherlands (grant number L17077 ) to A.H.C.; and the Jo Kolk study fund , the Netherlands to A.H.C.; and the Erasmus + Traineeship fund to A.H.C.; and the KNMP stipend , the Netherlands to A.H.C.
Funders | Funder number |
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Erasmus + | |
Jo Kolk study fund | |
Leiden International Study Fund | L17077 |
Erasmus+ |