Identification and use of agents that modulate oncogenic transcription agent activity

Abstract

Embodiments of the invention provides, among other things, methods for identifying agents that inhibit oncogenic transcription factors, induce apoptosis, inhibit the growth of transformed cells and cancer cells, and potentiate the effects of other agents that induce apoptosis and that inhibit the growth of transformed cells and cancer cells. Embodiments of the invention further provide compositions useful for the same comprising an agent the inhibits one or more oncogenic transcription factors and an agent that induces apoptosis, particular compositions wherein the apoptotic effect of the combination is greater than either agent by itself. Embodiments of the invention further provide for the use of such agents and compositions to treat cancer. In illustrative embodiments the agents that inhibit transcription factor activity are thiazole antibiotics, such as Siomycin and thiostrepton, and the apoptosis inducing agent is a member of the TNF ligand superfamily, such as TNF-alpha. In illustrative embodiments the cancers are those in which both the FoxM1 and the NF-kB oncogenic pathways are activated.