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Gene Warfare Against Melanoma


Developments to Watch: Antisense

Gene Warfare against Melanoma

For the first time, an "antisense" cancer agent has been shown to be effective in a human trial. Dr. Burkhard Jansen and colleagues at the University of Vienna said the treatment produced improvements in 6 of 14 patients with stage 4 melanoma, which is virtually untreatable.

Antisense treatments use engineered DNA-like molecules to disrupt the workings of genetic material in disease cells--and sensitize tumors to chemotherapy. In this case, a drug called G3139, made by Genta Inc. of Lexington, Mass., was given along with standard doses of chemotherapy over five days. The results: One 90-year-old woman went into complete remission. Two had remissions of more than 50%. Three had minor but measurable improvements, while four others were stabilized. The median survival rate for the patients in the trial is now nine months, Jansen says, compared with four to six months normally. "These results are very, very encouraging," says Peter Jones, director of the University of Southern California's Comprehensive Cancer Center. "This work should open the door to other treatments based on antisense." Jansen says Genta will begin a larger study within the next few months.Edited by Catherine ArnstReturn to top

Chemo without the Hair Loss?

While cancer experts can feel proud of their progress in improving the odds of surviving cancer, they still have a ways to go in reducing the nausea, pain, and hair loss that often accompany treatment. So there was great interest in Glaxo Wellcome Inc.'s new topical cream that helps prevent hair loss in rats undergoing chemotherapy.

Because the cells surrounding hair follicles divide rapidly, treatments that target rapidly proliferating malignant cells typically cause hair loss as well. Taxol, for example, a breast cancer treatment, can cause complete loss of all body hair. Stephen T. Davis and his Glaxo research team developed a synthetic compound, GW8510, meant to halt the activity of an enzyme involved in cell division called cyclin-dependent kinase 2 (CDK2). When applied to rats before treatments with the chemotherapy drug etoposide, the cream provided complete hair protection for half the animals and some protection for the other half. Says Davis: "It's quite rare to see such a visual effect." Dr. William N. Hiatt of the Cancer Institute of New Jersey said the research "could markedly improve the quality of life for patients." Glaxo now plans human trials, Davis said.Edited by Catherine ArnstReturn to top

What Guards a Smoker's Lungs

One of the great mysteries is why, of two people with identical risk factors for cancer, only one may develop the disease. The mystery deepens when it comes to smoking, for although 90% or more of lung cancer cases are tobacco-related, only 1 in 10 smokers develops cancer. What is protecting the rest of the puffers?

A research team led by Paul Lazarus of the H. Lee Moffitt Cancer Center in Tampa has come up with one possibility: an enzyme that removes from the body one of tobacco's most potent carcinogens, NNK--a byproduct of nicotine. NNK is removed from the body through the urine, along with various other toxins, by a family of enzymes known as UGTs. By examining various lung and liver tissues, researchers found that several UGTs are able to detoxify NNK, but only one, UGT2B7, is present in both the lungs and liver. This means, they say, that UGT2B7 rids the lungs of the effects of nicotine.

Researchers can now examine individuals' differences in the expression, or activity, of this enzyme--on the theory that smokers who have lower amounts of the enzyme may be at the highest risk of developing tobacco-related cancers.Edited by Catherine ArnstReturn to top


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