Triple-negative breast cancers (TNBCs) are a unique group of clinically aggressive breast cancers for which surgery and chemotherapy are the only available therapeutic modalities. Dr. Ed Liu and his lab, identified a genomic configuration called the tandem duplicator phenotype (TDP) that defines a major subgroup of TNBC. TDP tumors are initially highly sensitive to cisplatin. Despite their initial responsiveness, they develop resistance to cisplatin therapy. The challenge addressed by the proposed project is to test and validate an analysis pipeline to identify therapeutic interventions to reverse cisplatin resistance in TNBC. The objective is to apply structure-based control approaches to identify network node overrides in the form of multiple gene interventions that have the effect of reversing the development of resistance.