Histone deacetylase inhibitors (HDACi) are an emerging class of chemotherapeutic agents which induce growth arrest and cell death in tumor cells. The HDACi, SAHA, was recently approved for the treatment of cutaneous T-Cell lymphoma and is presently in trial for the treatment of colon cancer. Identification of patients likely to benefit from treatment with this agent is an important clinical challenge. By screening a panel of 30 colon cancer cell lines we have now identified cell lines highly sensitive and resistant to HDACi. Using gene expression microarrays we have identified a subset of genes whose induction in response to HDACi treatment is critical for response to this agent. The goal of this project is to identify the signaling pathways and transcription factor(s) which drive this transcriptional response. This knowledge could be highly informative in enabling clinicians identify cancer patients likely to benefit from this treatment.