Combinatorial drug screening identifies compensatory pathway interactions and adaptive resistance mechanisms.

ABSTRACT: Constitutively activated signaling molecules are often the primary drivers of malignancy, and are favored targets for therapeutic intervention. However, the effectiveness of targeted inhibition of cell signaling can be blunted by compensatory signaling which generates adaptive resistance mechanisms and reduces therapeutic responses. Therefore, it is important to identify and target these compensatory pathways with combinations of targeted agents to achieve durable clinical benefit. In this report, we demonstrate the use of high-throughput combinatorial drug screening as a discovery tool to identify compensatory pathways that generate resistance to the cytotoxic effects of targeted therapy. We screened 420 drug combinations in 14 different cell lines representing three cancer lineages, and

SUBMITTER: Axelrod M 

PROVIDER: S-EPMC3720609 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature