Predicting chemotherapeutic drug combinations through gene network profiling

摘要: Contemporary chemotherapeutic treatments incorporate the use of several agents in combination. However, selecting most appropriate drugs for such therapy is not necessarily an easy or straightforward task. Here, we describe a targeted approach that can facilitate reliable selection drug combinations through interrogation drug-resistance gene networks. Our method employed single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as model proliferating cells to delineate resistance network using synthetic lethality workflow. Using results previous unbiased screen, assessed genetic overlap doxorubicin with six other harboring varied mechanisms action. this model, drug-specific ontological sub-classifications were identified computation relative hypersensitivities. We found human gastric adenocarcinoma be sensitized by concomitant treatment cisplatin, intra-DNA strand crosslinking agent, and suberoylanilide hydroxamic acid, histone deacetylase inhibitor. findings point utility differential targeting conserved interaction when screening successful cells.