Personalized Multi-Drug Combinations in Breast Cancer Treatment Using Individual Pattern of Perturbed Gene Expression and Drug Signatures

The greatest challenge in recent years in cancer treatment has been drug screening. Few platforms presented reliable solutions for personalized drug validation and safety testing. Here, we constructed a personalized drug combination protocol as the primary input to such platforms. We used public data from whole-genome expression profiles of 6173 breast cancer patients, 312 healthy individuals, and 691 drugs. We developed an individual pattern of perturbed gene expression (IPPGE) for each patient. A protocol was designed to extract personalized drug combinations by comparing the IPPGE and drug signatures. We tried to use the concept of drug repurposing, which searches for the new benefits of the existing medicines that may perturb the desired genes. The potential for treatment effectiveness was more significant for drug combinations extracted from specialized and nonspecialized cancer medicines than specialized medicines. Thus, effective treatments can be provided through the approach of drug repurposing and combination drug therapy. Implications The protocol allows personalized drug combinations to be extracted from hundreds of drugs and thousands of drug combinations. This can be used as a methodological interface between drug repurposing and combination drug therapy in cancer treatment.