Cancer Drug Scores Again

Gleevec shows promise against bone tumor

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FRIDAY, Nov. 22, 2002 (HealthDayNews) -- The cancer drug commonly known as Gleevec shows early promise in pre-clinical trials against Ewing's sarcoma, a bone cancer in children and adolescents.

A study in the new issue of the Journal of the National Cancer Institute found that imatinib killed Ewing's sarcoma cells and shrunk tumors in mice.

This is the latest in a series of studies that show imatinib's promise in treating blood cancers and tumors.

National Cancer Institute researchers tested the drug in 10 mice with human Ewing's sarcoma tumors and in 10 Ewing's sarcoma cell lines.

Imatinib caused cell death in all 10 cell lines tested, including Ewing's sarcoma cells that are resistant to chemotherapy. The drug also blocked activation of the c-kit receptor tyrosine kinase, resulting in substantial tumor shrinkage in the mice with human Ewing's sarcoma tumors.

The study authors note that higher concentrations of imatinib were needed to kill Ewing's sarcoma cells than other tumor cells.

"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," the authors write.

In addition, new research released this week found that imatinib can increase the uptake of chemotherapy drugs by a tumor by blocking the action of growth factor on tumor stroma cells.

This finding could be an important advance in developing ways to improve the effectiveness of standard chemotherapy.

Tumor stroma cells are the connective tissue-like cells present in most kinds of solid tumors.

In studies with animals, Swedish researchers found that imatinib inhibited platelet-derived growth factor (PDGF) signaling and increased tumor uptake of cytotoxic (cell-killing) drugs twofold to fivefold.

There was no increase in the amount of cytotoxic drugs in normal tissue.

The studies used imatinib, which blocks PDGF signaling, in combination with either of the cytotoxic drugs 5-fluorouracil or paclitaxel, or with the experimental drug epothilone B.

In all cases, the combination therapy was more effective in treating tumors than the chemotherapy drugs alone.

The Swedish scientists plan to start human studies with the combination treatments early next year.

More information

Here's where you can learn more about cancer chemotherapy.

SOURCES: Journal of the National Cancer Institute, news release, Nov. 20, 2002; European Organization for Research and Treatment of Cancer, news release, Nov. 20, 2002

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