Getting melanoma chemotherapy to work.

People with the skin cancer called melanoma respond poorly to chemotherapy. Austrian researchers now report that a drug known as G3139 can turn off a gene that underlies this resistance. This gene, bcl-2, produces a protein that shields tumor cells from chemotherapy by thwarting the programmed cell death, or apoptosis, that these drugs induce in rapidly dividing cells.

G3139 is a mixture of synthesized DNA pieces "that basically glue themselves to RNA and prevent the Bcl-2 protein from being produced," says clinical pharmacologist Burkhard Jansen of the University of Vienna, who reported the findings.

Among 14 patients treated with chemotherapy and G3139 for advanced melanoma, remission occurred in one person, tumors shrank by more than half in two others, and tumors decreased somewhat less in another three, Jansen says. On average, the 14 patients survived 9 months after treatment, though patients with such advanced melanoma typically survive only 4 to 6 months.

Later this year, Jansen and his colleagues will begin testing the drug, made by Genta in Lexington, Mass., on 270 more melanoma patients in North America and Europe. Pancreatic and kidney tumors also produce the Bcl-2 protein, he says, making them possible targets for this drug.