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Researchers add piece to cancer drug resistance

By Wai Lang Chu , 26-Sep-2005

Researchers in the US have uncovered a contributing factor in interferon resistance of malignant melanoma cells. The finding represents a step forward in understanding of this type of cancer and the changes in gene and cellular signalling that trigger resistance to current therapies.

The use of interferon has become the most established immunotherapy for advanced-stage melanoma. Malignant melanoma itself is the deadliest form of skin cancer, and if not treated successfully can spread to affect the liver, lungs, or brain.

Chemotherapy fights the disease with limited efficiency and because of the inadequacy of this treatment; melanoma tumours often develop a resistance to the drug, posing one of the major obstacles in the clinical treatment of this cancer.

 

Scientists from the University of Wurzburg, have found that when a gene called STAT5 is too active in melanoma cells, it can counteract the anti-cancer effect of interferon.

 

Interferon normally impedes the growth of cancer cells, whereas STAT5 is thought to act to promote cellular growth.

 

The new work, published by Professor Manfred Schartl and Dr. Claudia Wellbrock in Current Biology, shows that interferon actually activates STAT5 in melanoma cells but that under normal conditions, this does not interfere with the inhibitory potential of the drug.

 

However, when cancer cells posses too much STAT5 activity to begin with, the further activation of STAT5 function by interferon induces a mechanism that blocks the ability of the drug to effectively inhibit growth.

 

Confirming this initial finding, the researchers found that when they inhibited STAT5 in interferon-resistant melanoma cells, they were able to restore the effectiveness of interferon.

 

This demonstrates the relevance of STAT5 and its contribution to the behaviour of melanoma cells in the late stage of the disease.

 

The findings explain the frequent failure of interferon therapies and thus further our understanding of melanoma in its late, and most aggressive, stage.

 

In the future, a routine analysis of the STAT5 status in melanoma patients might help to improve and personalize therapies.

 

Schartl and Wellbrock's work appears in the latest edition of Current Biology.

 

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