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Imatinib Mesylate (Gleevec; STI571) Monotherapy Is Ineffective in Suppressing Human Anaplastic Thyroid Carcinoma Cell Growth in Vitro

Thyroid Cancer Research Laboratory, Medical Service, Veterans Affairs Medical Center, Lexington, Kentucky 40511; and Department of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536-0298

Address all correspondence and requests for reprints to: Kenneth B. Ain, M.D., Thyroid Oncology Section, Division of Hematology and Oncology, Department of Internal Medicine, Room MN524, University of Kentucky Medical Center, 800 Rose Street, Lexington, Kentucky 40536-0298. E-mail: kbain1{at}uky.edu.

Imatinib mesylate is remarkably effective in treating chronic myeloid leukemia and metastatic gastrointestinal stromal tumors. Meanwhile, anaplastic thyroid carcinoma (ATC) remains a fatal malignancy for which there are currently no effective curative interventions. In chronic myeloid leukemia and gastrointestinal stromal tumors, imatinib inhibits the constitutive tyrosine kinase activity of BCR-ABL and c-KIT, respectively. Reports suggest that imatinib may also be effective against ABL and platelet-derived growth factor receptor kinase-dependent pathological conditions. These mechanisms provide a wide scope of possible clinical applications for the drug. Potentially, diseases instigated by constitutive kinase activity that can be inhibited with imatinib should be treatable with this drug. We evaluated the effects of imatinib on the viability, cycling, and tyrosine phosphorylation of ATC cells in vitro. Our data indicate that imatinib has negligible antineoplastic activity against ATC cell lines within established therapeutically useful concentrations. No constitutive kinase activity was detected in these cell lines that could be exploited as a therapeutic target by imatinib. We conclude that imatinib mesylate monotherapy would not be effective in ATC patients. Current preclinical data do not warrant future clinical studies of imatinib monotherapy for ATC.

Abbreviations: ATC, Anaplastic thyroid carcinoma; CML, chronic myeloid leukemia; GI₅₀, 50% growth inhibition; GIST, gastrointestinal stromal tumor; LC₅₀, concentration resulting in 50% lethality; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; PDGFR-ß, platelet-derived growth factor-ß receptor; TGI, total growth inhibition.

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