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Genetic Therapy: Proving Useful in Treating Some Cancers

Annual Report - 1997-1998

Dr. Jack A. Roth brought his dream for developing genetic therapy for human cancer when he joined the M. D. Anderson faculty in 1986 as chairman of the Department of Thoracic and Cardiovascular Surgery.

Today, he directs the most ambitious program for gene therapy and molecular therapeutics in the world. At the close of the fiscal year, 38 investigators from diverse basic science and clinical disciplines were involved in the translational research program.

"M. D. Anderson provides an unparalleled opportunity to conduct comprehensive clinical research. The faculty are fortunate to have superb institutional support and shared resources, which help us compete well for government grants and private funds," observes Dr. Roth, who holds the Bud Johnson Clinical Chair and also is a professor of tumor biology.

Dr. Roth's group described the first successful correction of a defective p53 tumor suppressor gene in advanced lung cancer in the September 1996 issue of Nature Medicine. This landmark report outlined how a retroviral vector, which doesn't cause human disease, was manipulated in the laboratory and used to inject normal p53 genes into the lungs of patients with non-small-cell lung cancer that had not responded to conventional therapies.

In an early (Phase I) clinical trial using an adenoviral vector to restore normal p53 function, 21 advanced lung cancer patients received the gene therapy. As anticipated, the study confirmed previous observations in experimental animals, which showed the technique was safe and did not cause any serious side effects. Each of the 21 patients received escalating doses of the p53 treatment once a month. Nine of them also were given intravenous doses of the drug cisplatin three days before being injected with the p53 gene.

While efficacy was not the primary goal of that first study, Dr. Roth and his colleagues were encouraged to find that treated tumors in five patients who received escalating doses of the p53 gene stopped growing and a sixth one had a partial response that lasted more than six months. In addition, the combined p53 gene and cisplatin treatments halted tumors from spreading for up to six months in eight patients.

The p53 gene injections also were studied in a Phase I clinical trial involving 33 patients with end-stage head and neck cancers. Dr. Gary L. Clayman, associate professor of head and neck surgery, directed this study, which was divided into two treatment groups.

He says one group of 18 patients received only the p53 gene injections, but a second group of 15 patients had surgery in addition to the gene therapy. Of the 15 patients undergoing surgery, five remained disease-free for more than six months.

"The latter group includes one patient who has been in remission just over two years and another man who has been free of disease for 21 months," Dr. Clayman says.

The longest-surviving head and neck cancer patient on the p53 gene therapy study is Elwood A. Mueller, who owns a ranch in Carmine in central Texas. To Dr. Clayman's delight, Mueller recently passed the two-year mark after taking the gene therapy regimen - and he also celebrated the 50th anniversary of being married to his wife, Bernice.

During the past year, Dr. Roth says more than 100 cancer patients were treated with the adenoviral p53 gene therapy method. Phase II trials began combining p53 gene replacement and radiation therapy for lung cancer patients. His technique is being applied to patients with prostate, bladder, liver and breast cancers.

Tests of other gene therapy approaches are under way for M. D. Anderson patients with breast and ovarian cancers and primary brain tumors.

© 2015 The University of Texas MD Anderson Cancer Center