Many studies have shown that a daily dose of aspirin can help prevent cancer. Now Sanford-Burnham scientists Dr. Xiao-kun Zhang, Dr. Hu Zhou and others have found a way to block tumor growth by using a related pain reliever called Sulindac. The study, published in the June 15, 2010 issue of the journal Cancer Cell, pieced together the molecular mechanism Sulindac uses to destroy cancer cells, and created a new-and-improved version of Sulindac that does an even better job of it.

According to the study, Sulindac targets RXRα, a receptor protein that carries signals into the nucleus to turn genes on and off. RXRα normally keeps cell growth in check. But Dr. Zhang and his colleagues noticed that many types of cancer cells carry RXRα’s evil twin – a truncated version that works with other proteins to keep cells growing, sometimes into tumors.  Fortunately, they also found that Sulindac blocks the mutant RXRα’s pro-survival function and prompts apoptosis, the process of cell suicide.

Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is currently marketed to treat pain, fever and arthritis. Similar NSAIDs have been pulled from the shelves in recent years because they were found to negatively affect the cardiovascular system. In this study, Dr. Zhang and colleagues fine-tuned Sulindac to make it easier on the heart and more effective at binding to RXRα. They called the new drug K-80003.

“Depending on the conditions, the same protein, such as RXRa, can either kill cancer cells or promote their growth,” Dr. Zhang said. “The addition of K-80003 shifts that balance by blocking survival pathways and sensitizing cancer cells to triggers of apoptosis.”