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

• Published in: The journal of clinical endocrinology and metabolism 2004-05, Vol.89 (5), p.2127-2135
• Main Authors: Dziba, Joshua M., Ain, Kenneth B.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Benzamides; Biological and medical sciences; Carcinoma - metabolism; Carcinoma - pathology; Cell Cycle - drug effects; Cell Division - drug effects; Cell Line, Tumor; Dose-Response Relationship, Drug; Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Genes, abl; Humans; Imatinib Mesylate; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oncogene Proteins - genetics; Phosphorylation - drug effects; Piperazines - administration & dosage; Piperazines - pharmacology; Proto-Oncogene Proteins c-abl - metabolism; Proto-Oncogene Proteins c-kit; Pyrimidines - administration & dosage; Pyrimidines - pharmacology; Receptor, Platelet-Derived Growth Factor beta - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Tyrosine - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-031734

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.