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Scientists identify protein critical to melanoma growth

BOSTON--Researchers at Dana-Farber Cancer Institute and Children's Hospital Boston have discovered that malignant melanoma, the potentially lethal skin cancer, can't grow without a steady supply of a protein that normal cells can do without.

The findings, which are published in the December issue of Cancer Cell, suggest that drugs that cut off melanoma cells' supply of the protein, called CDK2, might curb the growth of the dangerous skin cancer in patients, and with relatively low toxicity.

In theory, such a drug would leave normal cells unharmed and have many fewer side effects compared to standard chemotherapy.

Working with melanoma cells grown in the laboratory, the researchers, led by David E. Fisher, MD, PhD, Director of the Melanoma Program at Dana-Farber and the paper's senior author, showed that adding a chemical that quashed the activity of CDK2, the gene that manufactures CDK2 protein, dramatically slowed the growth and proliferation of the cancer cells. Unlike conventional chemotherapy drugs, a CDK2 inhibitor drug wouldn't be aimed at killing melanoma cells, only halting their growth.

Fisher said that CDK2-inhibiting drugs exist, and he hopes that the research results will soon lead to clinical trials of them in patients with melanoma.

The study's lead author is Jinyan Du, PhD, who carried out the project while working as a student in Fisher's lab at Dana-Farber. Fisher is also a pediatric oncologist at Dana-Farber/Children's Hospital Cancer Care.

The CDK2 gene and its protein (an enzyme) are one of several regulators of the cell cycle: That is, they help determine when a cell should be "resting" and when it should begin dividing to make more of itself. When cells become malignant, it is in part because their normal controls on growth and division are disabled, and they proliferate abnormally. Overactive CDK2 has been found in many types of cancer, making it a prime candidate for designer drugs that w
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Contact: Janet Haley Dubow
janet_haley@dfci.harvard.edu
617-632-5665
Dana-Farber Cancer Institute
20-Dec-2004


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