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Published on 15 May 2008

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Disabling protein weakens melanoma

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By targeting and disabling a protein frequently found in melanoma tumors, doctors may be able to make the cancer more vulnerable to chemotherapy, according to a new study by researchers in the Duke Comprehensive Cancer Center.

“We tested a compound that can weaken the tumor by targeting a protein expressed on the surface of a melanoma cell,” said Douglas Tyler, MD, a surgeon at Duke and the Durham Veterans Affairs Medical Center, and senior investigator on this study.

“When chemotherapy was applied to the tumor in this weakened state it was much more effective compared to conventional therapy alone.

“These results are extremely significant because they may help us better treat patients with this deadly condition.”

Although this study was done in laboratory rats, a clinical trial applying the same concept to humans has already begun at four comprehensive cancer centers nationwide, including Duke.

The researchers published their findings from the animal study in the 15 May issue of the journal Cancer Research.

After being implanted with melanoma tumors, rats were given a drug known as ADH-1, which makes it difficult for cells to bind properly to one another. The animals were then given one of two types of common chemotherapy drugs, melphalan and temozolomide.

“We found that the response to ADH-1 in combination with melphalan was more dramatic than the response to the drug in combination with temozolomide,” Tyler said. “The reason may be that the melphalan was infused directly into the affected area while temozolomide is given systemically.”

The researchers saw a 30-fold reduction in tumor size following treatment with ADH-1 and melphalan chemotherapy compared to chemotherapy alone. Tumor size shrunk about twofold in response to ADH-1 and temozolomide, Tyler said.

Duke Comprehensive Cancer Center



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