A large percentage of human cancers have high activity levels of an enzyme known as AKT. This enzyme controls a number of cell functions, including cell size, division and response to chemotherapy.
"The AKT signaling pathway is overly active in a wide variety of different cancers, including ovarian carcinoma, so we and others think that this pathway is an attractive target for cancer treatment at the molecular level," said Joseph Testa, Ph.D., director of the Human Genetics Program at Fox Chase. "However, because the AKT pathway is involved in so many cell processes, many of them beneficial, we were looking to control some of the proteins downstream from AKT so we didn't inhibit the good processes."
RAD001 is a derivative of rapamycin, a drug used as an immunosuppressant. RAD001 targets an enzyme known as mTOR (mammalian target of rapamycin). In mice injected with human ovarian cancer cells with high AKT activity, the researchers found that RAD001 arrested the cells so they couldn't divide (reproduce) or move to another location in the body (metastasize). The drug also reduced the cancer cells' ability to make blood vessels to nourish themselves (angiogenesis). In cancer cells with low levels of AKT activity, RAD001 had minimal effect.
Testa speculates that after being immobilized by RAD001, ovarian cancer cells could be vulnerable to chemotherapy that would kill the cells while their reproductive properties are weakened.
"Ovarian cancer is the leading cause of gynecologic cancer deaths," Testa said. "It usually isn't detected until it's quite advanced and is hard to treat. This is one drug that is well-tolerated and could be useful in ovarian cancer treatment."
Along with Testa, study authors are Fox Chase postdoctoral associate Seiji Mabuchi, M.D., Ph.D. and staff scientist Deborah Altomare, Ph.D.
Fox Chase Cancer Center was founded in 1904 in Philadelphia as the nation's first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu or call 1-888-FOX CHASE.