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New biomarker, therapeutic target for melanoma "truly exciting"
April 6, 2007
www.reutershealth.com
By Will Boggs, MD
NEW YORK (Reuters Health) - A member of the tumor necrosis factor receptor superfamily, TROY, may represent both a biomarker and a therapeutic target for melanoma, according to a report in the March 15th International Journal of Cancer.
"TROY may provide hope that a reliable and sensitive melanoma blood test may finally become a clinical reality," Dr. Remco A. Spanjaard told Reuters Health. "Additionally, TROY presents an exciting new target for therapy that is currently missing. As such, identification of TROY is truly an exciting discovery in our fight against melanoma."
Dr. Spanjaard and associates at Boston University School of Medicine, Massachusetts used murine S91 melanoma cells to search for novel melanoma-specific genes that may serve as biomarkers and therapeutic targets.
Genetic screening detected cDNA encoding TROY, and the investigators selected it for further study in other established cell lines.
None of 10 normal skin biopsies and none of 6 basal cell carcinoma specimens had detectable TROY expression, the researchers report, but all 45 primary and metastatic melanoma patient samples were TROY-positive with high levels of cytoplasmic expression in individual tumor cells.
TROY was co-expressed with TNF-receptor-associated factor-6 (TRAF-6) in 10 of 10 melanoma cases examined, the investigators say, "suggesting that the TROY--TRAF-6 signaling axis is likely functional in melanoma cells."
"A blood test that is sensitive and reliable enough to detect these circulating melanoma cells as an indicator of occult disease would be a fantastic method to achieve this goal of early detection," Dr. Spanjaard said.
"Another application of such a melanoma blood test is that you can monitor the response of established melanoma patients with metastatic disease to treatment by measuring changes in numbers of circulating melanoma cells before and after treatment," Dr. Spanjaard added.
The team found that DNA replication was reduced by about 50% in cells depleted of TROY, the report indicates, further suggesting an important role for TROY in the growth of melanoma cells.
"With TROY we now also have a new target on melanoma to attack the disease directly rather than indirectly," Dr. Spanjaard pointed out. "We are currently discussing these plans with other industrial partners who would have the resources to rapidly propel this work forward."
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