A major obstacle in the effective treatment of chordoma is that there are no 
identifiable biomarkers capable of predicting prognosis. Recent research has 
indicated that signal transducers and activators of transcription (Stat3) may be 
an important prognostic marker in some cancers, but its role in chordoma tumors 
has not been elucidated. In this study, the expression of Stat3 was evaluated in 
chordoma tissue microarray that contains 70 chordoma samples. Cells in the 
tissue microarray showed nuclear staining for phosphorylated Stat3 in all 
instances. The level of phosphorylated Stat3 expression correlated with the 
survival and severity of the disease. Three chordoma cell lines were exposed to 
SD-1029, a novel inhibitor of Stat3 activation. MTT assay showed that the growth 
of all chordoma cell lines was inhibited by SD-1029. The expression of Stat3 
signaling cascade was inhibited in all chordoma cell lines after treatment with 
SD-1029. The cytotoxicity of the combination of SD-1029 and chemotherapeutic 
drugs is significantly better than either agent alone. Phosphorylation of Stat3 
in chordoma cells in vitro and cellular proliferation in three-dimensional 
culture were inhibited by SD-1029. In conclusion, the Stat3 pathway is 
constitutively activated in chordomas and the level of expression may serve as a 
predictor for prognosis. Blockade of the Stat3 pathway represents a potential 
strategy for future treatment.