Imatinib is a tyrosine kinase inhibitor that has produced high response rates in patients with chronic myelogenous leukemia and gastrointestinal stromal tumors. Both cancers are associated with the overactivation of a specific tyrosine kinase. In Ewing's sarcoma, overactivation of the c-kit receptor tyrosine kinase contributes to tumor growth and tumor cell proliferation.
Melinda S. Merchant, M.D., Ph.D., of the National Cancer Institute, and her colleagues examined whether imatinib inhibited tumor growth and cell proliferation of Ewing's sarcoma by testing the drug in 10 mice bearing human Ewing's sarcoma tumors and in 10 Ewing's sarcoma cell lines.
Treatment with imatinib caused cell death in all cell lines tested, including those resistant to chemotherapy. "This observation is especially important because chemoresistance is a major contributor to the rate of treatment failure in recurrent Ewing's sarcoma," the authors say. Treatment with imatinib also blocked activation of the c-kit receptor tyrosine kinase and resulted in substantial tumor shrinkage in mice bearing human Ewing's sarcoma tumors.
The authors note that higher concentrations of imatinib were needed to kill Ewing's sarcoma cells than other tumor cells but that "even if the toxicity of higher doses of imatinib proves intolerable for clinical translation of these results, the identification of the target or targets of imatinib that lead to cytotoxicity in Ewing's sarcoma may allow the design of related compounds with increased specificity to induce death of Ewing's sarcoma cells."
Contact: Linda Wang
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Journal of the National Cancer Institute
19-Nov-2002