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Scientists uncover a new gene therapy-targeting strategy for treating head and neck cancers
By Bijal P. Trivedi

Researchers have identified a difference between cancerous and healthy cells that line the human mouth and throat. The finding could be exploited to create targeted gene therapy treatments for head and neck cancers.

A receptor protein called hCAR is present on the surface of tumor cells but not on the surface of healthy differentiated mouth epithelial cells. Adenovirus, a virus that is often used by gene therapy researchers to deliver therapeutic genes, uses the hCAR receptor as a gateway into the cell. Cells without hCAR cannot be infected, which means that only tumor cells would be vulnerable to adenovirus infection. The results are published in the November 20th issue of Human Gene Therapy.

Wendell Yarbrough and his colleagues at the University of North Carolina at Chapel Hill believe that normal cells lacking hCAR form a barrier that prevents adenovirus from reaching and infecting the cancer cells and delivering therapeutic genes.

A precancerous condition known as cellular dysplasia, in which the cells are abnormal but also express the hCAR receptor, would also be vulnerable to adenovirus.

"So, theoretically, in people at high risk for cancer, adenoviral gene therapy would only infect the pre-cancerous [and cancerous] sites and leave the normal, well-differentiated sites alone," Yarbrough was quoted as saying.

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Yarbrough, W. G. Efficiency of adenovirus-mediated gene transfer to oropharyngeal epithelial cells correlates with cellular differentiation and human coxsackie and adenovirus receptor expression. Hum Gene Ther 11, 2365-2375 (November 20, 2000).

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