Identification of a Triple Drug Combination That Is Synergistically Cytotoxic for Triple-Negative Breast Cancer Cells Using a Novel Combination Discovery Approach.

ABSTRACT: Triple-negative breast cancer (TNBC) is a very aggressive form of breast cancer with few molecularly targeted therapies. We used a novel unbiased approach to identify higher-order synergistic or enhancer combinations of marketed kinase inhibitor drugs that inhibit cell viability of TNBC cell lines. We mixed all 33 kinase-targeted drugs on the market at the time of this study, which allowed for all possible combinations to exist in the initial mixture. A kinase inhibitor group dropout approach was used to identify active groups and then single active drugs. After only three rounds of deconvolution, we identified five single drugs to test further. After further testing, we focused on one novel subset consisting of three kinase inhibitor drugs: dasatinib, afatinib, and trametinib (DAT) that t

SUBMITTER: Ahmad S 

PROVIDER: S-EPMC8293681 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature