Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism

Oncotarget
Muhammad KashifM G Gustafsson

Abstract

We analyzed survival effects for 15 different pairs of clinically relevant anti-cancer drugs in three iso-genic pairs of human colorectal cancer carcinoma cell lines, by applying for the first time our novel software (R package) called COMBIA. In our experiments iso-genic pairs of cell lines were used, differing only with respect to a single clinically important KRAS or BRAF mutation. Frequently, concentration dependent but mutation independent joint Bliss and Loewe synergy/antagonism was found statistically significant. Four combinations were found synergistic/antagonistic specifically to the parental (harboring KRAS or BRAF mutation) cell line of the corresponding iso-genic cell lines pair. COMBIA offers considerable improvements over established software for synergy analysis such as MacSynergy™ II as it includes both Bliss (independence) and Loewe (additivity) analyses, together with a tailored non-parametric statistical analysis employing heteroscedasticity, controlled resampling, and global (omnibus) testing. In many cases Loewe analyses found significant synergistic as well as antagonistic effects in a cell line at different concentrations of a tested drug combination. By contrast, Bliss analysis found only one type of si...Continue Reading

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Apr 24, 2014·Molecular Cancer Therapeutics·Muhammad KashifMats G Gustafsson

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Methods Mentioned

BETA
pharmacotherapy

Software Mentioned

COMBIA
CompuSyn
mixlow
[UNK]
COMBIA ( COMBination Interaction Analysis )
CalcuSyn
R
hbim
R package
R package synergyfinder

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