Gene Therapy

Scientists have found that a gene therapy, invented at The University of Texas M. D. Anderson Cancer Center, increases the rate of survival for patients having head and neck cancer in the end-stage.

This therapy, involving Advexin(r), a modified adenovirus that expresses the tumor-suppressing gene p53, for end-stage head and neck cancer, has been the first to succeed in a U.S. phase III clinical trial for cancer by Introgen Therapeutics, Inc.

"Cells become cancerous because p53 no longer functions. Restoring p53 works unlike any current cancer treatment because it treats the cancer genome," said Jack Roth, M.D., professor in M. D. Anderson's Department of Thoracic & Cardiovascular Surgery, who invented the drug and co-founded Introgen.

Many types of cancer involve the inactivation of the p53 gene, while normally it halts the division of a defective cell and then force the cell to kill itself.

The trial showed that p53 expression in the patient's tumor before treatment is a reliable biomarker for how to treat head and neck cancer.

It was observed that patients with a favourable p53 profile who received Advexin(r) had a median survival of 7.2 months, as against 2.7 months for those whose tumor expressed high levels of mutant p53 before treatment. Those having this unfavourable profile were better off taking the chemotherapy drug methotrexate, resulting in median survival of 5.9 months.

"The important finding is that patients who benefit from treatment can be identified with the p53 biomarker. The biomarker will enable physicians to personalize treatment," said Roth, who also directs M. D. Anderson's W.M. Keck Center for Innovative Cancer Therapies.

The trial led by John Nemunaitis, M.D., executive director of the Mary Crowley Medical Research Center at Baylor-Charles A. Sammons Cancer Center in Dallas, was conducted on 123 patients.

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

"That certainly results in a better quality of life," noted Roth.

And this appears to be relevant as p53 does not cause problems in normal cells. And now 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. 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," said Roth.