The Burnham Institute’s Jeffrey Smith, Ph.D., has discovered that orlistat, commonly prescribed as an anti-obesity drug, has a positive side-effect: it inhibits cancer growth. Dr. Smith made this discovery using an activity-based proteomics screening technique developed in his laboratory that makes it possible to identify active targets and simultaneously screen for their inhibitors. 
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 designed a proteomics screen based on monitoring the activity of a family of enzymes—serine hydrolyases—involved in metabolism. They used their screen to compare normal prostate cells with <<>> cells and discovered that the proteomics cells are affected by an increased activity of fatty acid synthase. Fatty acid synthase is the enzyme that converts dietary carbohydrate to fat.
The screen also identified orlistat, marketed by Roche as Xenical™, as an inhibitor of fatty acid synthase.
These discoveries, made in vitro, held true when tested in mice. When they administered orlistat to mice bearing prostate tumors, the Smith laboratory discovered that the drug was able to inhibit tumor growth. Further experiments confirmed that orlistat has no effect on normal prostate cells and no apparent side effects in the mice; it acts specifically on fatty acid synthase.
Additional screening of breast cancer and colon cancer cells revealed that fatty acid synthase activity is upregulated in these tumors, as well, presenting the possibility of designing new treatments for these cancers based on inhibiting the enzyme’s activity with orlistat or a new drug based on orlistat’s inhibitory activity.
Orlistat was originally developed as an inhibitor of pancreatic lipase. Pancreatic lipase is a member of the same enzyme family--the serine hyrdolases—used in Smith’s screening. It is involved in processing of fats in the digestive tract, which is how the drug prevents adsorption of dietary fat.