Novel open source software for drug combination analysis reveals complex effects of combining clinically used drugs

The study, published in the scientific journal Oncotarget, reveals complex concentration-dependent synergistic and antagonistic interactions between clinically used drugs for colon cancer when the cancer cells are cultured in test tubes.

More and more individuals are treated with multiple drugs that will hopefully be more powerful in combination than alone. However, basic research has been hindered by the lack of readily available methods for identifying promising combinations. In a recent article in Oncotarget, Dr Muhammad Kashif and colleagues report a novel open source software package for drug combination analysis called COMBIA. The software is based on robust statistics for drug synergy analysis developed in a team at the Department of Medical Sciences led by Professor Mats Gustafsson.

In the article, the software is used to reveal complex patterns of synergy/antagonism in colon cancer cells exposed to different combinations of clinically used drugs. An interesting finding was the presence of both synergistic and antagonistic effects of the same clinical drug combinations, but at different concentration ranges. This suggests that more effective treatment can be achieved by taking greater care in the selection of anti-cancer drug combinations and doses.

Complex patterns of synergy and antagonism are discernible in COMBIA analyses due to its in-built robustness originating from the use of non-parametric statistical analysis. The analysis takes into account the fact that the experimental errors are dependent on the magnitudes of the collected data (heteroscedasticity) and also performs controlled resampling and global (omnibus) testing. This means that COMBIA provides multiple improvements compared with established academic and commercial software available for drug combination synergy analysis.