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| |  Diabetes Drug Troglitazone Slows Tumour Cells Growth BOSTON, MA -- March 30, 1999 -- In a study that points the way to a new form of cancer therapy, researchers at Dana-Farber Cancer Institute and Harvard Medical School report that a drug commonly used to treat diabetes has caused tumour cells to shift to a slower-growing, less-menacing state in patients with a rare type of cancer. The study, published in today’s issue of The Proceedings of the National Academy of Sciences, is the first to demonstrate that so-called differentiation therapy -- which prods tumour cells to return to the path of normal development and maturation, where they grow and divide more slowly -- can be effective in patients with solid tumours. The study is the result of basic laboratory research that began at Dana-Farber in the 1980s. "Our team's previous work showed that the diabetes drug troglitazone could cause laboratory samples of liposarcoma cells to mature, or differentiate," said the study's lead author, George Demetri, M.D., of Dana-Farber. (Liposarcoma is a rare cancer that occurs in fat cells.) "This study shows that the same results can be achieved in patients with advanced cases of liposarcoma. It's an exciting example of a technique that works in the laboratory being directly applicable to people with disease." The research report describes three patients, all women, each of whom had liposarcoma. They took troglitazone in pill form every day and their health was monitored regularly. At the end of six to eight weeks, biopsies were taken of the women's tumour cells and compared with tumour cells taken at the start of the study. In each case, the patients' cancer cells were found to be more fully differentiated -- and proliferating less actively -- than they had been at the study's start. The degree of differentiation was determined by analysing cells' microscopic structure, biochemical composition, and pattern of gene activation. Troglitazone therapy was continued daily as long as the disease remained stable. In addition to the three patients described in detail in the study, other liposarcoma patients have had good results with troglitazone therapy. The report notes that a second group of patients who have taken troglitazone also show evidence that their tumour cells have become more fully differentiated. Demetri said that while troglitazone therapy did not cause any of the patients' tumours to shrink, the fact that it did trigger differentiation in the cancer cells opens enticing prospects for the further development of this new approach to cancer therapy. While noting that much needs to be done to refine the progress made thus far, Singer explained that differentiation therapy could one day take its place as an adjunct to surgery and other conventional treatments for solid tumours. Because other types of cancer cells, including most colon cancers and many types of breast and prostate cancers, have PPARg receptors, troglitazone may well be able to spur differentiation in those diseases as well. Clinical studies are now under way to determine whether they can.
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