Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation. Medium-throughput results were scrutinized and extensively analyzed for sensitivity patterns, synergy, anticancer activity, and were validated in low-throughput experiments. Principal component analysis revealed that a fraction of all upregulated or downregulated genes of a particular targeted pathway could partly explain cell sensitivity toward agents targeting that pathway. Combination therapies deemed immediately tractable to translation in

SUBMITTER: Wali VB 

PROVIDER: S-EPMC5582957 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature