title: Imatinib mesylate (gleevec; STI571) monotherapy is ineffective in suppressing human anaplastic thyroid carcinoma cell growth in vitro.
abstract: 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.
authors.affiliation: Thyroid Cancer Research Laboratory, Medical Service, Veterans Affairs Medical Center, Lexington, Kentucky 40511, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Dziba
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Ain
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001549:Benzamides; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D015513:Oncogene Proteins / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015513:Oncogene Proteins; D010879:Piperazines; D011743:Pyrimidines; D014443:Tyrosine; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta; D016315:Proto-Oncogene Proteins c-abl