Grants to fund GIST Research

October 15, 2006: The Liddy Shriver Sarcoma Initiative is proud to announce that it has awarded two grants of $5,000 each to help fund gastrointestinal stromal tumor (GIST) research in the laboratory of Dr. Sebastian Bauer at the West German Cancer Center at the University Hospital in Essen, Germany, and the laboratory of Dr. Anette Duensing at the Hillman Cancer Center at the University of Pittsburgh Cancer Institute.

These monies were, in large part, the result of the fund raising efforts of Team GIST which took part in the Team Sarcoma 2006 Initiative. We would like to express our thanks to GIST Support International for taking the lead in forming Team GIST and are pleased to be partnering with them in making this grant possible.

Dr. Bauer noted that:

Imatinib has greatly improved the treatment of patients with metastatic GIST. However, 20% of patients exhibit primary resistance and the majority of patients who respond to imatinib eventually progress. For these patients, alternative treatment strategies are urgently needed. While the mechanisms of early or primary resistance to imatinib remain unclear, several mechanisms have been identified for patients with secondary resistance. Among those are additional mutations in the imatinib binding area, which reduce the ability of imatinib to bind and inhibit KIT.

Current research is focused on alternative KIT-Inhibitors or inhibitors of KIT-depending signaling intermediates. Some groups are focused on the evaluation of potential therapeutically relevant inhibitors of KIT. Among those are direct and indirect KIT-inhibitors, which need to be extensively evaluated to enable their future use in patients.

Dr. Bauer told us that the Liddy Shriver Sarcoma Initiative’s research grant will help to co-finance PhD student Thomas Mühlenberg who currently evaluates an indirect approach to inhibit KIT. This approach may be helpful to overcome the problem of secondary mutations in imatinib-resistant GIST. In addition, funds will be used to partly defray costs for media for cell culture experiments as well as antibodies to test the molecular effects of the new treatments.

Dr. Duensing told us that her research funds will be used to:

further elucidate the precise mode of action of imatinib mesylate (Gleevec). Imatinib is a potent small molecule kinase inhibitor that is very successful in the treatment of GIST. However, imatinib is not a cure, and unfortunately many patients acquire resistance to this drug over time. Identifying the exact mechanism of action of imatinib will be instrumental for the development of alternative treatment approaches for patients with primary or recurrent GISTs and novel strategies to circumvent imatinib resistance. We have shown that a molecule that is known to be involved in DNA double strand break repair is massively overexpressed in GIST cells after imatinib treatment. Further experiments revealed that the upregulation of this protein is critically involved in the induction of GIST cell death (apoptosis). We will expand these findings using various GIST cell line models as well as a GIST tissue microarray.