RAD001 from Novartis is an orally available derivative of the compound rapamycin, found over 30 years ago in soil bacteria from Easter Island (called Rapa Nui in the native language). First tried as an antifungal, it was later approved as an immunosuppressant for organ transplants, blocking the proliferation of cells that cause rejection. Studies in the 1970s hinted at potential anticancer properties, but research was slow.
Later, rapamycin was found to inhibit an important kinase that was named mTOR (mammalian Target Of Rapamycin), a signal transduction molecule, downstream from the KIT kinase pathway. The mTOR pathway plays a role in normal cellular growth, proliferation and survival. The hope is that some cancers dependent on an overactive mTOR pathway might respond to a safe inhibitor.
More recently, for Gastrointestinal Stromal Tumor (GIST) resistant to the KIT inhibitor Gleevec, the idea of trying Gleevec in combination with RAD001 to further block of the downstream mTOR kinase pathway was proposed for clinical trial investigation.
RAD001 (everolimus) in combination with Gleevec for advanced GIST patients was studied in a small clinical trial in Belgium by Dr. Allan van Oosterom. Initial Phase I data was presented at the 2004 ASCO Annual Meeting:
http://www.asco.org/ac/1,1003,_12-002511-00_18-0026-00_19-009415,00.asp
Initial results did not show significant effectiveness; however, shortly after the 2004 ASCO meeting Dr. Charles Blanke responded: "Dr. Allan van Oosterom presented data on RAD001, which theoretically is a very attractive drug that plays well with imatinib preclinically. He only presented Phase I data, and, as you would expect from a Phase I trial, there were no response data. But we also believe that the drug was not given in the most optimal fashion, and that if it were given daily, there would be more of an angiogenic effect. I do hope to see a benefit in the Phase II portion of the studies. All we can say right now is that it remains a promising drug but there is no way to say if it will work yet."
U.S. Clinical Trials information for other (currently, non-GIST) RAD001 trials may be found at:
http://www.clinicaltrials.gov/ct/gui/search?term=RAD001
http://www.clinicaltrials.gov/ct/gui/search?term=everolimus
