Applying synergy metrics to oncology combination screening data: agreements, disagreements and pitfalls

Item Type:	Review
Title:	Applying synergy metrics to oncology combination screening data: agreements, disagreements and pitfalls
Creators Name:	Vlot, A.H.C. and Aniceto, N. and Menden, M.P. and Ulrich-Merzenich, G. and Bender, A.
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.
Keywords:	Antineoplastic Combined Chemotherapy Protocols, Biological Models, Drug Synergism, High-Throughput Screening Assays, Neoplasm Drug Resistance, Neoplasms, Tumor Cell Line
Source:	Drug Discovery Today
ISSN:	1359-6446
Publisher:	Elsevier
Volume:	24
Number:	12
Page Range:	2286-2298
Date:	December 2019
Official Publication:	https://doi.org/10.1016/j.drudis.2019.09.002
PubMed:	View item in PubMed

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