Central targets of 5-fluorouracil (5FU) resistance.

We used a model cellular system with paired sensitive and resistant cell lines to study transcriptomic changes associated with drug resistance to the chemotherapeutic agent 5-fluorouracil (5-FU). We identified activation of ISG (interferon-stimulated genes) as a major component of 5-FU resistance, including Ifit3. A second major aspect of 5-FU resistance was mobilization of Xist via Dlx2. A third component of 5-FU resistance was activation of nucleotide synthesis through TYMS and the TYMSOS. 5-FU resistance was associated with a major change in cellular identity defined by Sp9 induction.