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Gene therapy increases survival for end-stage head and neck cancer
Date:5/28/2008

mmons Cancer Center in Dallas, are available at www.introgen.com.

Better Quality of Life

Patients treated with Advexin experienced far fewer harmful side effects such as pneumonia than those who received methotrexate. The incidence of inflammation of the mouth lining and a decrease in white blood cells, for example, both dropped to zero for those receiving Advexin.

"That certainly results in a better quality of life," Roth noted, which makes sense because p53 does not cause problems in normal cells.

Roth's lab has been developing gene therapy for cancer since 1990. "We wanted to go beyond conventional treatment, because most of those treatments were not very effective," Roth said. "Surgery and radiation are limited to the local tumor and once given, it's very hard to repeat those therapies. Chemotherapy inhibits DNA replication, but it also interferes with normal cells."

From idea to Phase I Trial at M. D. Anderson

All basic and preclinical work on the modified adenovirus was done at M. D. Anderson. The first phase I clinical trial was conducted by Gary Clayman, M.D., D.D.S., professor in M. D. Anderson's Department of head and neck surgery. Clayman also enrolled patients in the phase II and phase III clinical trials conducted by Introgen.

Roth and colleagues deleted an important region of the adenovirus' genome, preventing it from replicating. They installed a genomic segment that expresses p53. When injected into a tumor, the p53 adenovirus burrows into the cancer cell's nucleus. But instead of replicating in a typical viral manner, it expresses p53, resulting in cell death.

Clayman's phase I trial provided the first indicator that p53 expression in the tumor before treatment could be an accurate biomarker for p53 therapy. The concept was further developed retrospectively in Introgen's phase II trial, Roth said, and then it was applied prospe
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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