| Gastrointestinal Stromal Tumors and Hsp90
Disease background and scientific rationale
Gastrointestinal stomal tumors (GIST) is a life threatening type of sarcoma that is highly resistant to traditional cytotoxic chemotherapy or radiation treatment. The American Cancer Society estimates that between 4,500 and 6,000 Americans develop GIST each year.
In the majority of GIST cases, there are specific mutations in cellular signaling enzymes (“kinases”) called KIT or platelet-derived growth factor receptor-alpha (PDGFRA) which are responsible for the growth and survival of the tumor. Targeted kinase inhibitors target these enzymes and have dramatically improved disease control and survival for patients with GIST. However, resistance to kinase inhibitors is an emerging problem, necessitating the development of new drugs with novel mechanisms of action.
Both KIT and PDGFRA are also client proteins of Hsp90, and in preclinical experiments are degraded in cancer cells upon treatment with retaspimycin, also known as IPI-504, leading to cancer cell death. These data suggest that Hsp90 inhibition with retaspimycin is a promising area for clinical investigation. Furthermore, with a complementary, novel mechanism of action, inhibition of Hsp90 has the potential to aid in overcoming resistance to kinase inhibitor therapy.
Clinical trials
Preliminary data from Infinity’s open-label, dose-escalation Phase 1 clinical trial of retaspiycin hydrochloride in patients with metastatic and/or unresectable GIST were presented at the American Society of Clinical Oncology (ASCO) 2007 Annual Meeting in June 2007. The data presented showed that 16 of 21 evaluated patients (76%) had a best response of Stable Disease as measured by RECIST (Response Evaluation Criteria in Solid Tumors).
- Click here for more information on Infinity’s ongoing clinical trial in GIST.
Infinity and MedImmune have been granted orphan drug designation for retaspimycin by both the U.S. Food and Drug Administration’s Office of Orphan Products Development and the European Medicines Agency Committee for Orphan Medicinal Products for the treatment of GIST.
To help you learn more about GIST, we have provided links to the following GIST support groups:
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