Vitamin A Compound Helps Fight Cancer in Smokers

In a study of heavy smokers, researchers at The University of Texas M. D. Anderson Cancer Center have discovered that a synthetic vitamin A compound significantly reduces the activity of telomerase, an enzyme vital to the development and growth of cancer. Dr. Li Mao, associate professor of thoracic/head and neck medical oncology and the study's principal investigator, discussed his findings at a news conference during the American Association for Cancer Research meeting held in New Orleans. The study's lead author, Dr. Jean-Charles Soria, an M. D. Anderson post-doctoral fellow in thoracic/head and neck medical oncology, further reported the findings during the scientific meeting.

"To my knowledge, this is the first set of data to provide promising evidence that a molecular biomarker may sensitively measure the effectiveness of a chemopreventive agent in the lung," said Dr. Mao, who is also the director of M. D. Anderson's molecular biology laboratory.

In the double-blind study of 57 heavy smokers who had no evidence of cancer, 27 participants were randomly assigned to receive the chemopreventive agent and synthetic retinoid N-(4-hydroxphenyl) retinamide (4-HPR). The remaining 30 subjects received a placebo. Lung biopsies from all participants were obtained from six predetermined sites in the bronchial tree before and after the six-month treatment period.

Using the biopsies to measure the effectiveness of 4-HPR and to determine the role of telomerase in early lung cancer development, the researchers further analyzed TERT, the catalytic subunit of telomerase, as a biomarker.

Dr. Mao said studying TERT as a biomarker was significant because in past studies, telomerase activity has been evident in up to 90 percent of human lung cancer cells but is rare in normal, healthy cells. Dr. Mao explained that telomerase prolongs the aging process of a cell. The longer cells live, the more often they divide, leading to an increased risk that the cells will accumulate genetic abnormalities - such as deletion of a tumor-suppressor genes - making it possible for once-normal cells to become malignant.

At the baseline of the study, the expression of TERT was similar in both groups: 62.4 percent in participants taking 4-HPR compared to 65.3 percent in participants taking the placebo. However, after six months, only 45.6 percent of the biopsies expressed TERT in the 4-HPR group in contrast to 68.1 percent in the placebo group.

"The modulation of TERT expression under the effect of 4-HPR gives insight into a new molecular mechanism underlying the retinoid's chemopreventive properties," said Dr. Mao. "Furthermore, with this study, the utilization of TERT expression shows promise as a biomarker for risk assessment and efficacy evaluation of chemopreventive agents in the lung."

Dr. Waun Ki Hong, chairman of M. D. Anderson's Department of Thoracic/Head and Neck Medical Oncology and a co-author of the study, underscored the significance of the findings.

"The success of the molecular biomarker in measuring the efficacy of a chemopreventive agent such as 4-HPR paves the way for future research and offers us a tremendous new lead in future studies involving lung cancer chemoprevention," said Dr. Hong, who assumed the presidency of the 15,000-member American Association for Cancer Research during the annual meeting.

Chemoprevention is a burgeoning discipline with roots at M. D. Anderson. Using drugs or other compounds to prevent or interrupt the cancer process, chemoprevention research is under way at M. D. Anderson in studies involving colon, lung and breast cancers. M. D. Anderson researchers were the first to show that retinoids can reverse oral leukoplakia, a precancerous condition that can lead to head and neck cancer.

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©2006 Texas Medical Center

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