In this study, AECC investigators Huang, Horwitz, Goldberg, Smith, and collaborators examined the role of the insulin-like growth factor (IGF) signaling pathway in the response of ovarian cancer cells to Taxol and evaluated the significance of this pathway in human epithelial ovarian tumors. A Taxol-resistant cell line, HEY-T30, was developed from the HEY ovarian cancer line to study the drug-resistant phenotype. These investigators found that Taxol-induced AKT phosphorylation required IGF1R tyrosine kinase activity and was associated with upregulation of IGF2. Resistant cells had higher IGF2 expression compared with sensitive cells, and inhibition of the IGF pathway restored sensitivity to Taxol. High IGF2 tumor expression correlated with advanced stage (p<0.001) and tumor grade (p<0.01), and reduced disease-free survival (p<0.05). These studies indicate that IGF2 modulates Taxol resistance, and that inhibition of the IGF pathway sensitized drug-resistant cells to Taxol. The data suggest further that tumor IGF2 expression is a candidate prognostic biomarker in epithelial ovarian tumors and that IGF2 represents a therapeutic target in ovarian cancer, particularly in the setting of Taxol resistance.