HSP90 inhibitor IPI-504 from Infinity has completed phase I testing at five sites in the United States and Canada. HSP-90 is a protein that acts as a chaperone for other proteins during cell stress conditions— a condition often found within inflamed and necrotic tumors. IPI-504 acts by maintaining client protein conformation thereby protecting the client protein from the cell’s natural housekeeping functions. One of the client proteins protected by HSP-90 is mutant c-KIT in GIST. By inhibiting HSP- 90, IPI-504 allows the cell to identify and destroy mutant c-KIT. According to Infinity, the more mutant the client the more effective the HSP-90 inhibition and the greater the opportunity for the cell’s self-cleaning process to work. In theory, IPI-504’s effect is also mutationindependent.

Dr. Andrew Godwin, a researcher at Fox Chase Cancer Center in Philadelphia, Penn., presented data at the 2008 American Society of Clinical Oncology conference (ASCO) indicating that the Insulin-like Growth Factor 1 Receptor (IGF-1R) may have a role in GIST oncogenesis. Up to now, most research has focused on the mutant c- KIT or PDGFRα proteins that have been identified as the initiating pathogenic event in over 80 percent of GIST tumors. However there has always been five to ten percent of GIST that have no mutation and are called "Wild-type". While some of these GISTs have responded to c-KIT inhibitors, it is clear that another mechanism has been involved in their growth. Godwin’s research focused on these wild-type tumors, which occur in adults but also mainly in female, pediatric GIST patients.