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.