Obesity Drugs May Fight Cancer

Jeffrey Smith, Ph.D. of the Burnham Institute in California published his results of his study in a 2004 issue of Cancer Research in which he claims a commonly prescribed anti-obesity drug many inhibit cancer growth. The metabolism of a tumor cell is different from its normal counterpart cell. Scientists have long suspected that metabolism is connected to tumor progression. Dr. Smith and co-workers compared normal prostate cells with prostate cancer cells and discovered that the prostate cancer cells are affected by an increased activity of fatty acid synthase. Fatty acid synthase is the enzyme that converts dietary carbohydrate to fat. The researchers then identified orlistat, a common anti-obesity drug marketed by Roche as XenicalTM, as an inhibitor of fatty acid synthase.

The initial research was done in vitro and then extended to mice studies. When they administered orlistat to mice bearing prostate tumors, the Smith laboratory discovered that the drug was able to inhibit tumor growth in mice. Further experiments confirmed that orlistat has no effect on normal prostate cells and no apparent side effects in the mice; it acts specifically as fatty acid synthase.

Additional screening of breast cancer and colon cancer cells revealed that fatty acid synthase activity is unregulated in these tumors as well. These findings, while preliminary,  open the door to designing new treatments for these cancers based on inhibiting the enzyme's activity with drugs that inhibits its activity.  

"This discovery with orlistat has given us a very nice wedge with which we can go in and perturb tumor cells and ask the question, 'What are the active targets, what are the other changes that take place when you inhibit fatty acid synthase?'", says Dr. Smith, "and that will give us really good insights into the mechanism, and we anticipate that's going to reveal a whole swath of additional drug targets along this pathway. This is a big advance in the sense that we have an approved drug--approved for one indication--that has another target and another potential disease indication, prostate cancer."

Dr. Smith is Associate Scientific Director for Technology at The Burnham Institute, where he is also an Associate Professor in the Institute's NCI-designated Cancer Center.

Co-authors contributing to this study include Drs. Steven J. Kridel and Fumiko Axelrod, postdoctoral fellows at The Burnham Institute, and Dr. Natasha Rozenkrantz of Activix Biosciences in La Jolla.


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