Drug wrecks the power plants of cancer cells

Researchers have identified a compound that selectively kills tumor cells by destroying their metabolic power plants. The researchers believe that the compound, code-named F16, could serve as a model for a targeted chemotherapy with low toxicity.

In an article published in the July 2002 issue of the journal Cancer Cell, researchers led by Howard Hughes Medical Institute senior investigator Philip Leder at Harvard Medical School reported that they screened 16,000 small molecules to look for compounds that would have a favorable effect on transgenic mouse cells engineered to overexpress the cancer-causing gene neu. The human counterpart of neu, which is called HER-2, has been implicated in 20-30 percent of human breast cancers, and is linked with a poor prognosis for breast cancer treatment.

"Because neu or its human analog are such important elements in breast cancer, we decided to carry out these experiments to identify metabolic pathways that might collaborate with HER-2 or neu in the development of malignancy," said Leder.

In the experiments, the paper's lead author, HHMI associate Valeria R. Fantin, introduced the neu gene into mouse mammary epithelial cells. Mouse mammary epithelial cells that overexpress neu bear some of the characteristics of human breast tumors. Fantin then tested each of the 16,000 molecules to see how it affected the growth of the transgenic and normal mouse cells. These studies showed that F16 selectively inhibited the growth of the neu-overexpressing cells, but not the normal cells.

Additional studies indicated that F16 also inhibited the proliferation of a number of mouse cancer-cell lines that were derived in Leder's laboratory and a panel of human breast cancer cell lines. The researchers found that F16 prevented the formation of tumors that would normally occur when '"/>

Contact: Jim Keeley
Howard Hughes Medical Institute

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