Inactivation of the tumor suppressor p53 or constitutive activation of stress response proteins (e.g. NF-kB or HSF-1 and other heat shock proteins) are frequently found in many types of cancers. Such changes are often associated with poor response to chemotherapy and, thus, decreased survival. Curaxins are a novel class of multifunctional antitumor agents that simultaneously target all three of these pathways. Comparison of the efficacy and accumulation of Curaxins in tumors will enable us to prioritize these drugs (e.g. most effective against resistant tumors preferable for lead). The significance of this proposal lies in the ability of our compounds to simultaneously target multiple pathways frequently associated with poor treatment response and thus has broad applicability to many cancer types.
