Specific inhibition of heat-shock-protein 90 (Hsp90) by a novel peptidomimetic inhibitor shepherdin in malignant glioma cells

• Applicant: Professor Dr. Markus David Siegelin
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 125479995

Malignant gliomas are the most common type of brain tumors. The most common and malignant form of gliomas is known as glioblastoma multiforme (GBM), which accounts for approximately 60%–70% of the cases. Current standard-of-care therapy for GBM confers a median survival period of only 14.6 months. Heat-shock-protein 90 (Hsp90) is an attractive therapeutic target since it can bind a number of well-characterized client proteins, including many oncogenic signaling proteins being essential for progression and therapeutic resistance of GBM such as ErbB2, EGFR, Raf, MEK, PDGFR, Cdk-4, - 6, and -9, Akt, mutated p53 and survivin. Many of these proteins are the ones that are mutated or overexpressed in GBM. A novel specific inhibitor of Hsp90 is the peptidomimetic Shepherdin that has been shown to specifically target tumour cells whereas it has no effect on non-neoplastic cells. In this study Shepherdin will be evaluated as a potential new drug in treating GBM.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Dario C. Altieri